PDF (827 KB) - ACS Publications - American Chemical Society

May 23, 2019 - 2H), 7.39−7.35 (m, 1H), 7.28−7.25 (m, 1H), 7.02−6.98 (m,. 2H), 4.14−3.94 (m, 4H), 3.87 (s, 3H), 1.21 (t, J = 7.2 Hz,. 6H); 13C{...
3 downloads 0 Views 790KB Size
Download PDF
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Article Cite This: ACS Omega 2019, 4, 9049−9055

http://pubs.acs.org/journal/acsodf

Mn(III)-Mediated C−H Phosphorylation of Indazoles with Dialkyl Phosphites Payel Ghosh, Susmita Mondal, and Alakananda Hajra* Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India

Downloaded via 188.68.1.21 on July 19, 2019 at 18:14:50 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: A direct and efficient Mn(III) acetate-mediated phosphorylation of 2H-indazoles with dialkyl phosphites has been achieved under mild reaction conditions. A series of phosphorylated products with a wide range of functional groups were obtained in moderate to good yields. A radical mechanism has been proposed for the present protocol.

■

INTRODUCTION Organophosphorus compounds are an important class of organic compounds, exclusively applicable in organic synthesis,1 material sciences, 2 medicinal chemistry,3 agro industry,4 and coordination chemistry.5 The chemical and physical properties of parent molecules are changed by the incorporation of the phosphate group. Many P-containing heterocycles show excellent biological activities.6 Moreover, phosphonate esters are frequently used as prodrugs in the pharmaceutical industry.7 Therefore, development of newer methodologies for introducing the phosphonate esters into organic molecules is highly demanding in organic synthesis. First, in 1980 Hirao and coworkers described palladiumcatalyzed phosphorylation of aryl iodides or bromides.8 After that, many cross-coupling reactions between aryl (pseudo)halides, aryltriflates, tosylates, boronic acids, aryl diazonium salts, alkenyl/alkynyl carboxyl acids, or nucleophilic heteroarenes and H-phosphonates or H-phosphine oxides have been developed using transition-metal catalysts.9 However, recently direct oxidative C−H phosphorylation using transition-metalcatalyst has drawn much attention to the organic synthetic chemist. Indazole, a N-containing heterocyclic compound, acts as efficient bioisosteres of indole and benzimidazole in pharmaceutical chemistry.10 It has gained considerable attention in pharmaceuticals due to their broad range of biological activities11 like antitumor,11a antimicrobial,11b antiinflammatory,11c antidepressant,11d anti platelet,11e anticancer,11f and HIV-protease inhibition.11g Indazoles are used as estrogen receptors, bacterial gyrase β-inhibitors11h and also have potential activity towards the imidazoline I2-receptor and 5-HT1A receptors. It is the core structure of many drug molecules12 such as MK-4827 (anticancer agent), pazopanib, bendazac (votrient, tyrosine kinase inhibitor), and gamendazole (Figure 1). Owing to their high biological activities, various methodologies have been made for the synthesis13 and © 2019 American Chemical Society

Figure 1. Some biologically active 2H-indazole-containing molecules.

functionalization14 of indazoles. Our group was also actively involved for functionalization of 2H-indazoles.15 Very recently, our group reported phosphorylation of 2H-indazole with diphenylphosphine oxide via visible light photoredox catalysis.15b But in our previous conditions15b phosphonate ester did not react with 2H-indazole. It is worthy to mention that Mn(III) acetate is found to be an effective catalyst for various C−H functionalization.16,17 Considering the high importance of both phosphonate esters and indazole moiety, herein we describe a direct C−H phosphorylation of 2H-indazole with dialkyl phosphites using manganese(III) acetate at 80 °C (Scheme 1). Received: April 18, 2019 Accepted: May 9, 2019 Published: May 23, 2019 9049

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

Scheme 1. Phosphorylation of Indazoles

■

RESULTS AND DISCUSSION To optimize the phosphorylation of 2H-indazole, we commenced our study by taking 2H-indazole (1a) and diethyl phosphite (2a) as model substrates. At first, the reaction was carried out using 2 equiv Mn(OAc)3·2H2O in CH3CN at 80 °C. Interestingly, diethyl (2-phenyl-2H-indazol-3-yl)phosphonate (3aa) was formed in 52% yield after 10 h (Table 1, entry 1). The yield of the reaction did not improve

acetate is not suitable for such transformation (Table 1, entry 11). Moreover the reaction did not proceed in the absence of Mn(III) acetate (Table 1, entry 12). Other catalysts like Cu(acac)2, MnO2, CuI, and Fe(acac)3 were unable to produce the desired product (Table 1, entries 13−16). Finally, we got the optimized reaction conditions using 2 equiv Mn(OAc)3· 2H2O and 2 equiv diethyl phosphite in AcOH at 80 °C for 10 h (Table 1, entry 2). After optimizing the reaction conditions, we explored the substrate scope to study the generality of this protocol (Scheme 2). A series of phosphorylated 2H-indaozoles were

Table 1. Optimization of the Reaction Conditions for Phosphorylation of Indazolesa

Scheme 2. Substrate Scopea

entry

catalyst (2 equiv)

solvent (2 mL)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)3·2H2O Mn(OAc)2 _ Cu(acac)2 MnO2 CuI Fe(acac)3

CH3CN AcOH EtOH NMP 1,2-DCE DMF AcOH AcOH AcOH AcOH AcOH AcOH AcOH AcOH AcOH AcOH

52 88 trace 32 35 21 41c 82d 81e 58f NR NR NR NR NR NR

a Reaction conditions: 1a (0.2 mmol), catalyst (2 equiv), diethyl phosphite (2 equiv), and solvent (2 mL) for 10 h at 80 °C. bIsolated yield. cThe reaction was performed using 1 equiv and, dThe reaction was performed using 3 equiv Mn(III) acetate at 80 °C. eThe reaction was conducted at 100 °C and. fThe reaction was conducted at 60 °C. NR = no reaction.

Reaction conditions: 1 (0.2 mmol), Mn(OAc)3·2H2O (2 equiv), diethyl phosphite (2a, 2 equiv), and AcOH (2 mL) for 10 h at 80 °C. b On a 5 mmol scale. a

even after 12 h. Encouraged by this initial result, the reaction was carried out under different conditions to optimize the reaction and the results are summarized in Table 1. Initially, we checked the solvent effect taking other different solvents like AcOH, EtOH, NMP, 1,2-DCE, and DMF (Table 1, entries 2− 6). Better results were obtained in AcOH providing the desired phosphorylated product in 88% yield (Table 1, entry 2). The yield was dropped to 41% with diminishing the amount of Mn(III) acetate (1 equiv) but no improvement of yield was observed with the increase in load of Mn(III) acetate (3 equiv) as well as diethyl phosphite (3 equiv) (Table 1, entries 7 and 8). The reaction yield did not increase significantly at 100 °C but the yield was diminished to 58% with lowering the reaction temperature (60 °C) (Table 1 entries 9 and 10). Mn(II)

synthesized in moderate to good yields under the present reaction conditions. First, we examined the effect of the different N-2 substituents on 2H-indazoles. Electron-donating groups like −Me and −OMe substituted 2H-indazoles reacted very smoothly under optimized reaction conditions (3ba− 3ea). Halogen substituted 2-phenyl-2H-indazoles also produced the phosphorylated product in good yields (3fa−3ja). In addition, 2-(naphthalen-1-yl)-2H-indazole also worked well (3ka). However, ortho-substituted 2-phenyl-2H-indazoles, Nalkyl, and N-benzyl substituted 2-H-indazole were not suitable for this reaction. Moreover, 1H-indazole and unprotected 2H9050

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

phosphorylation reaction is completely suppressed with the addition of radical scavengers like, 2,6-di-tert-butyl-4-methyl phenol, 2,2,6,6-tetramethylpiperidine-1-oxyl, and p-benzoquinone. These results suggest a radical mechanism of the present reaction Scheme 5.

indazole remained unreactive towards the phosphorylation reaction. In addition, 1H-pyrazolo[3,4-d]pyrimidin-4-amine and 1H-pyrazole did not respond in this reaction. Furthermore, the gram-scale reaction was carried out under the normal laboratory set up using 2-phenyl-2H-indazole (1a, 5 mmol) and diethyl phosphite (2a, 10 mmol) under the standard reaction conditions. Delightfully, the reaction offered the corresponding product (3aa) with comparable yield (82%) which clearly elucidates the practical applicability of this present methodology. Next, we checked the effect of different substituents at the arene part of 2H-indazoles (Scheme 3). Halogen (−F and

Scheme 5. Radical Trapping Experiments

Scheme 3. Substrate Scope of Indazolea In accordance with the control experimental results and previous literature reports,17 we proposed a plausible mechanism of phosphorylation reaction in Scheme 6. At first, Scheme 6. Probable Mechanism

Reaction conditions: 1 (0.2 mmol), Mn(OAc)3·2H2O (2 equiv), diethyl phosphite (2a, 2 equiv), and AcOH (2 mL) for 10 h at 80 °C.

a

−Cl) containing substrates efficiently reacted with diethyl phosphite to produce the desired products in good yields (3la−3na). 5-Methoxy-2-(4-methoxyphenyl)-2H-indazole and diethyl 5-methoxy-2-(p-tolyl)-2H-indazole also reacted effectively under the optimized reaction conditions to form the desired products in good yields (3oa and 3pa). With the optimized conditions, the scope of this protocol was also extended with different phosphorylating agents (Scheme 4). Dimethyl phosphite and diisopropyl phosphite effectively reacted with differently substituted 2H-indazoles to provide the phosphorylated products in moderate to good yields (3ab, 3bb, 3bc, and 3mc). But diphenyl phosphite, dibenzyl phosphite, diphenylphosphine oxide, and triethyl phosphite were unable to produce the desired products. Finally, radical trapping experiments were conducted to probe the mechanistic pathway of this reaction. The present

phosphoryl radical (A) is formed by Mn(III) acetate. Then, addition of the phosphoryl radical A at the C-3 position of 2Hindazole (1a) provides the intermediate B. The elimination of the hydrogen radical from intermediate B gives the desired C− H phosphorylated product 3aa.

■

CONCLUSIONS In summary, we have established a convenient, efficient, and simple method for the C(sp2)−H phosphorylation of 2Hindazoles using dialkylphosphites as phosphorylating agent in the presence of Mn(OAc)3·2H2O. This protocol is featured with regioselectivity, high functional group tolerance, simple reaction conditions, and scalability. Based on our experimental result, a radical mechanistic pathway has been suggested. To the best of our knowledge, we are not aware of any earlier

Scheme 4. Substrate Scope of Phosphonate Estera

Reaction conditions: 1 (0.2 mmol), Mn(OAc)3·2H2O (2 equiv), dialkyl phosphite (2, 2 equiv), and AcOH (2 mL) for 10 h at 80 °C.

a

9051

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

was added to the reaction mixture and stirred at 80 °C for 10 h. After completion of the reaction (TLC), the reaction mixture was quenched with sodium bicarbonate solution (5 mL). The reaction mixture was then extracted with ethyl acetate. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get the crude residue which was purified by column chromatography on silica gel (60−120 mesh) using petroleum ether/ethylacetate = 80:20 as an eluant to afford the pure product diethyl (2phenyl-2H-indazol-3-yl)phosphonate (3aa) (55.44 mg, 84%) as a colorless liquid. Diethyl(2-phenyl-2H-indazol-3-yl)phosphonate (3aa). Colorless liquid (84%, 55.44 mg); Rf = 0.5 (PE/EA = 80:20); 1 H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.8 Hz, 1H), 7.86−7.83 (m, 1H), 7.68−7.66 (m, 2H), 7.53−7.50 (m, 3H), 7.41−7.37 (m, 1H), 7.30−7.27 (m, 1H), 4.13−3.93 (m, 4H), 1.18 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.7 (d, J = 17.0 Hz), 141.0, 129.2 (d, J = 82.0 Hz), 128.4 (d, J = 19.0 Hz), 127.0, 126.4, 124.8 (d, J = 13.0 Hz), 122.7, 121.4, 119.9, 118.3, 62.9 (d, J = 6.0 Hz), 16.1 (d, J = 8.0 Hz); 31P NMR (162 MHz CDCl 3 ): δ 4.72; Anal. Calcd for C17H19N2O3P: C, 61.81; H, 5.80; N, 8.48%. Found: C, 61.60; H, 5.84; N, 8.59%. Diethyl(2-(p-tolyl)-2H-indazol-3-yl)phosphonate (3ba). White solid (86%, 59.16 mg); Rf = 0.55 (PE/EA = 70:30); mp 88−89 °C; 1H NMR (400 MHz, CDCl3): δ 8.45− 8.43 (m, 1H), 8.19−8.16 (m, 1H), 7.89−7.87 (m, 2H), 7.72− 7.70 (m, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.61−7.59 (m, 1H), 4.46−4.29 (m, 4H), 2.78 (s, 3H), 1.54 (t, J = 7.2 Hz, 6H); 13 C{1H} NMR (100 MHz, CDCl3): δ 148.7 (d, J = 16.0 Hz), 139.7, 138.5, 129.4 (d, J = 13.0 Hz), 128.4 (d, J = 18.0 Hz), 126.9, 126.1, 124.7 (d, J = 15.0 Hz), 122.5 (d, J = 21.0 Hz), 118.3, 115.5, 62.8 (d, J = 5.0 Hz), 21.3, 16.1 (d, J = 7.0 Hz); 31 P NMR (162 MHz CDCl3): δ 4.89; Anal. Calcd for C18H21N2O3P: C, 62.78; H, 6.15; N, 8.14%. Found: C, 62.97; H, 6.18; N, 8.05% Diethyl(2-(m-tolyl)-2H-indazol-3-yl)phosphonate (3ca). Yellow liquid (88%, 60.54 mg); Rf = 0.45 (PE/EA = 75:25); 1H NMR (400 MHz, CDCl3): δ 8.12−8.10 (m, 1H), 7.85−7.82 (m, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.41−7.36 (m, 2H), 7.32−7.27 (m, 2H), 4.14−3.94 (m, 4H), 2.44 (s, 3H), 1.19 (t, J = 7.2 Hz, 6H); 13C{1H}NMR (100 MHz, CDCl3): δ 148.6 (d, J = 17.0 Hz), 140.9, 138.9, 130.3, 128.5 (d, J = 6.0 Hz), 128.3, 126.9 (d, J = 2.0 Hz), 124.7, 124.6, 123.4, 122.6, 121.4, 118.3, 62.8 (d, J = 5.0 Hz), 21.3, 16.1 (d, J = 6.0 Hz); 31 P NMR (162 MHz CDCl3): δ 4.82; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C18H21N2O3PNa, 367.1182; found, 367.1183. Diethyl(2-(4-methoxyphenyl)-2H-indazol-3-yl)phosphonate (3da). Brown gummy mass (86%, 61.92 mg); Rf = 0.45 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.4 Hz, 1H), 7.84−7.81 (m, 1H), 7.60−7.56 (m, 2H), 7.39−7.35 (m, 1H), 7.28−7.25 (m, 1H), 7.02−6.98 (m, 2H), 4.14−3.94 (m, 4H), 3.87 (s, 3H), 1.21 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.4, 148.6 (d, J = 16.0 Hz), 134.0, 128.3 (d, J = 18.0 Hz), 127.6, 126.9, 124.7 (d, J = 28.0 Hz), 122.7, 121.3, 118.2, 113.8, 77.3, 62.8 (d, J = 5.0 Hz), 55.7, 16.2 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.96; Anal. Calcd for C18H21N2O4P: C, 60.00; H, 5.87; N, 7.77%. Found: C, 60.15; H, 5.82; N, 7.87%. Diethyl(2-(3-methoxyphenyl)-2H-indazol-3-yl)phosphonate (3ea). Yellow liquid (84%, 60.48 mg); Rf =

report of direct phosphorylation of the 2H-indazole moiety with phosphonate esters. We believe this direct C−P bond formation strategy will achieve significant importance in material sciences, pharmaceutical chemistry, and also in organic synthesis.

■

EXPERIMENTAL SECTION General Information. All reagents were received from commercial sources, unless specified otherwise. Dried and distilled solvents were used. All reactions involving moisture sensitive reactants were performed using oven dried glassware. 1 H NMR spectra were recorded on a 400 MHz spectrometer, 13 C{1H} and 31P NMR spectra were determined at 100 and 162 MHz, respectively, in CDCl3 solution. Chemical shifts as the internal standard were referenced to CDCl3 (δ = 7.26 for 1 H and δ = 77.16 for 13C{1H} NMR) and expressed in ppm. Coupling constants (J) are expressed in hertz (Hz). The following abbreviations were used to explain the multiplicities: s (singlet), d (doublet), dd (doublet of doublet), t (triplet), m (multiplet), and q (quartet). Thin layer chromatography was carried out by using thin-layer chromatography (TLC) plates (silica-gel-coated glass slide) with eluants hexane-ethyl acetate and the reaction was monitored under UV radiation. All the derivatives of 2H-indazole were prepared by the reported methods.13d,14c,15d Compounds 1a,13d 1b,13d 1c,15d 1d,14c 1f,15d 1g,13d 1h,14c 1i,15d 1j,14c 1l,13d 1m,13d 1o,15d and 1p15d are known, and the spectroscopic and physical data are completely matched with those from the literature. 2-(3-Methoxyphenyl)-2H-indazole (1e). Yellow liquid (92%, 618.24 mg); Rf = 0.50 (PE/EA = 93:07); 1H NMR (400 MHz, CDCl3): δ 8.33 (d, J = 0.4 Hz, 1H), 7.82−7.80 (m, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.52 (t, J = 2.4 Hz, 1H), 7.41−7.30 (m, 3H), 7.11−7.08 (m, 1H), 6.92−6.89 (m, 1H), 3.85 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.5, 149.6, 141.5, 130.2, 126.8, 122.6, 122.4, 120.5, 120.4, 117.8, 113.8, 112.7, 106.7, 55.5; Anal. Calcd for C14H12N2O: C, 74.98; H, 5.39; N, 12.49%. Found: C, 75.16; H, 5.30; N, 12.58%. 2-(Naphthalen-1-yl)-2H-indazole (1k). Brown solid (83%, 607.5 mg); Rf = 0.45 (PE/EA = 98:02); mp 85−86 °C; 1H NMR (400 MHz, CDCl3): δ 8.31 (d, J = 0.8 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.87−7.84 (m, 1H), 7.80−7.78 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.68− 7.66 (m, 1H), 7.61−7.48 (m, 3H), 7.41−7.37 (m, 1H), 7.21− 7.17 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.7, 134.3, 129.8, 129.2, 127.7, 127.5, 126.9, 126.7, 125.6, 125.1, 124.0, 123.1, 122.5, 122.2, 120.5, 118.1; Anal. Calcd for C17H12N2: C, 83.58; H, 4.95; N, 11.47%. Found: C, 83.71; H, 5.00; N, 11.37%. 5-Chloro-2-phenyl-2H-indazole (1n). Yellow solid (90%, 615.6 mg); Rf = 0.50 (PE/EA = 97:03); mp 79−80 °C; 1H NMR (400 MHz, CDCl3): δ 8.25 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 9.2 Hz, 1H), 7.58 (s, 1H), 7.44 (t, J = 8.0 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 7.17−7.15 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.2, 140.3, 129.7, 129.4, 128.3, 128.2, 123.2, 121.0, 120.1, 119.6, 119.1; Anal. Calcd for C13H9ClN2: C, 68.28; H, 3.97; N, 12.25%. Found: C, 68.09; H, 3.94; N, 12.30%. Typical Experimental Procedure for the Compound Diethyl(2-phenyl-2H-indazol-3-yl)phosphonate (3aa). A mixture of 2-phenyl-2H-indazole (1a) (0.2 mmol 38.8 mg), diethylphosphite (2a, 2 equiv, 55.2 mg), and Mn(OAc)3·2H2O (2 equiv, 107.2 mg) was taken in a reaction tube. Then, AcOH 9052

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

0.45 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 8.12 (d, J = 8.4 Hz, 1H), 7.86−7.83 (m, 1H), 7.42−7.36 (m, 2H), 7.29−7.26 (m, 3H), 7.06−7.04 (m, 1H), 4.13−3.97 (m, 4H), 3.86 (s, 3H), 1.20 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.7, 148.6 (d, J = 16.0 Hz), 141.9, 129.4, 128.4 (d, J = 18.0 Hz), 127.0, 124.7 (d, J = 12.0 Hz), 122.6, 121.4, 118.5, 118.3, 115.8, 111.8, 62.8 (d, J = 6.0 Hz), 55.6, 16.1 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.82; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H22N2O4P, 361.1312; found, 361.1311. Diethyl(2-(4-fluorophenyl)-2H -indazol-3-yl)phosphonate (3fa). Brown liquid (74%, 51.50 mg); Rf = 0.50 (PE/EA = 75:25); 1H NMR (400 MHz, CDCl3): δ 8.08−8.06 (m, 1H), 7.84−7.81 (m, 1H), 7.67−7.63 (m, 2H), 7.42−7.38 (m, 1H), 7.30−7.27 (m, 1H), 7.23−7.17 (m, 2H), 4.14−3.95 (m, 4H), 1.22 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.3, 161.7 (d, J = 33.0 Hz), 148.8 (d, J = 17.0 Hz), 137.1, 132.7, 128.3 (d, J = 9.0 Hz), 126.2 (d, J = 211.0 Hz), 125.1, 124.7 (d, J = 48.0 Hz), 121.6 (d, J = 8.0 Hz), 119.8 (d, J = 302.0 Hz), 115.7 (d, J = 23.0 Hz), 77.3, 63.0 (d, J = 5.0 Hz), 16.2 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.65; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C17H18FN2O3PNa, 371.0931; found, 371.0925. Diethyl(2-(4-chlorophenyl)-2H-indazol-3-yl)phosphonate (3ga). Yellow liquid (85%, 61.88 mg); Rf = 0.55 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 8.10− 8.07 (m, 1H), 7.85−7.82 (m, 1H), 7.66−7.62 (m, 2H), 7.51− 7.48 (m, 2H), 7.42−7.38 (m, 1H), 7.31−7.27 (m, 1H), 4.16− 3.97 (m, 4H), 1.23 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.9 (d, J = 16.0 Hz), 139.5, 135.6, 129.0, 128.4 (d, J = 19.0 Hz), 127.7, 127.3, 125.0, 122.9, 121.3, 118.3, 63.0 (d, J = 5.0 Hz), 16.2 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.57; Anal. Calcd for C17H18ClN2O3P: C, 55.98; H, 4.97; N, 7.68%. Found: C, 55.80; H, 5.01; N, 7.63%. Diethyl(2-(3-chlorophenyl)-2H-indazol-3-yl)phosphonate (3ha). Brown liquid (81%, 58.96 mg); Rf = 0.45 (PE/EA = 80:20); 1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.4 Hz, 1H), 7.85−7.82 (m, 1H), 7.73 (t, J = 2.0 Hz, 1H), 7.62−7.59 (m, 1H), 7.51−7.38 (m, 3H), 7.31−7.27 (m, 1H), 4.16−4.00 (m, 4H), 1.23 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.9 (d, J = 16.0 Hz), 141.9, 134.4, 130.0, 129.7 (d, J = 7.0 Hz), 128.5 (d, J = 18.0 Hz), 127.4, 126.8, 125.0, 124.7, 122.9, 121.4, 118.3, 63.0 (d, J = 5.0 Hz), 16.2 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.38; Anal. Calcd for C17H18ClN2O3P: C, 55.98; H, 4.97; N, 7.68%. Found: C, 56.19; H, 5.02; N, 7.76%. Diethyl(2-(4-chloro-3-fluorophenyl)-2H-indazol-3-yl)phosphonate (3ia). Brown gummy mass (82%, 62.64 mg); Rf = 0.45 (PE/EA = 85:15); 1H NMR (400 MHz, CDCl3): δ 8.09−8.07 (m, 1H), 7.84−7.78 (m, 2H), 7.62−7.58 (m, 1H), 7.43−7.38 (m, 1H), 7.31−7.27 (m, 2H), 4.19−4.00 (m, 4H), 1.25 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.6 (d, J = 51.0 Hz), 148.9 (d, J = 16.0 Hz), 137.4 (d, J = 3.0 Hz), 129.0, 128.5, 128.3, 127.5, 126.4 (d, J = 8.0 Hz), 125.1, 121.3, 118.3, 116.7, 116.5, 77.3, 63.1 (d, J = 6.0 Hz), 16.2 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.40; HRMS (ESITOF) m/z: [M + Na]+ calcd for C17H17ClFN2O3PNa, 405.0542; found, 405.0541. Diethyl(2-(4-bromophenyl)-2H-indazol-3-yl)phosphonate (3ja). Light yellow liquid (79%, 64.62 mg); Rf = 0.45 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 8.09−8.07 (m, 1H), 7.84−7.82 (m, 1H), 7.67−7.64 (m, 2H), 7.60−7.56 (m, 2H), 7.42−7.38 (m, 1H), 7.31−7.27 (m, 1H),

4.15−3.99 (m, 4H), 1.23 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.9 (d, J = 16.0 Hz), 140.0, 137.9, 131.9, 128.4 (d, J = 18.0 Hz), 128.0 (d, J = 14.0 Hz), 127.3, 124.9, 123.2 (d, J = 89.0 Hz), 121.3, 118.3, 63.0 (d, J = 5.0 Hz), 16.2 (d, J = 6.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.57; Anal. Calcd for C17H18BrN2O3P: C, 49.90; H, 4.43; N, 6.85%. Found: C, 50.07; H, 4.49; N, 6.91%. Diethyl(2-(naphthalen-1-yl)-2H-indazol-3-yl)phosphonate (3ka). Brown gummy mass (73%, 55.48 mg); Rf = 0.50 (PE/EA = 75:25); 1H NMR (400 MHz, CDCl3): δ 8.21−8.19 (m, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.95−7.88 (m, 2H), 7.67−7.65 (m, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.54−7.50 (m, 1H), 7.47−7.39 (m, 2H), 7.36−7.33 (m, 1H), 7.06 (d, J = 8.0 Hz, 1H), 3.95−3.68 (m, 4H), 1.34−1.07 (m, 3H), 0.79− 0.76 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.8 (d, J = 16.0 Hz), 137.1, 133.8, 132.3, 130.5 (d, J = 9.0 Hz), 127.9 (d, J = 19.0 Hz), 127.6, 127.2, 126.8, 126.4, 125.5, 125.1, 124.8, 124.5, 122.8, 121.5, 118.4, 77.3, 76.9, 62.7 (d, J = 5.0 Hz), 16.1 (d, J = 7.0 Hz), 15.6 (d, J = 3.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.11; Anal. Calcd for C21H21N2O3P: C, 66.31; H, 5.56; N, 7.36%. Found: C, 66.18; H, 5.53; N, 7.25%. Diethyl(5-fluoro-2-(p-tolyl)-2H-indazol-3-yl)phosphonate (3la). Yellow liquid (85%, 61.54 mg); Rf = 0.45 (PE/EA = 85:15); 1H NMR (400 MHz, CDCl3): δ 7.83−7.79 (m, 1H), 7.69 (dd, J = 2.4 Hz, 9.6 Hz, 1H), 7.54−7.52 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.20−7.15 (m, 1H), 4.13−3.93 (m, 4H), 2.44 (m, 3H), 1.20 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.0 (d, J = 242.0 Hz), 146.0 (d, J = 16.0 Hz), 139.9, 138.5, 129.4, 128.5 (d, J = 12.0 Hz), 128.3 (d, J = 12.0 Hz), 126.0, 120.5 (d, J = 10.0 Hz), 118.6 (d, J = 29.0 Hz), 104.3 (d, J = 26.0 Hz), 62.9 (d, J = 5.0 Hz), 21.3, 16.1 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.58; Anal. Calcd for C18H20FN2O3P: C, 59.67; H, 5.56; N, 7.73%. Found: C, 59.52; H, 5.52; N, 7.83%. Diethyl(5-fluoro-2-phenyl-2H-indazol-3-yl)phosphonate (3ma). Yellow liquid (81%, 56.37 mg); Rf = 0.45 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 7.84− 7.80 (m, 1H), 7.71 (dd, J = 9.6 Hz, 2.4 Hz, 1H), 7.68−7.65 (m, 2H), 7.54−7.51 (m, 3H), 7.22−7.17 (m, 1H), 4.13−3.93 (m, 4H), 1.19 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.0 (d, J = 243.0 Hz), 146.1 (d, J = 16.0 Hz), 140.8, 129.7, 128.8, 126.3, 120.5 (d, J = 10.0 Hz), 118.9, 118.6, 104.5, 104.2, 62.9 (d, J = 5.0 Hz), 16.1 (d, J = 6.0 Hz); 31P NMR (162 MHz CDCl 3 ): δ 4.43; Anal. Calcd for C17H18FN2O3P: C, 58.62; H, 5.21; N, 8.04%. Found: C, 58.81; H, 5.27; N, 7.96%. D i e t h y l ( 5 - c h l o r o - 2 - p h e n y l -2H - i nd azo l -3- y l ) phosphonate (3na). Yellow liquid (82%, 59.69 mg); Rf = 0.50 (PE/EA = 75:25); 1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 2.0 Hz, 1H), 7.79−7.77 (m, 1H), 7.67−7.65 (m, 2H), 7.54−7.51 (m, 3H), 7.33 (dd, J = 9.2 Hz, 2.0 Hz, 1H), 4.12− 3.96 (m, 4H), 1.19 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 147.1 (d, J = 15.0 Hz), 140.8, 130.7, 129.8, 128.9 (d, J = 16.0 Hz), 128.6, 126.3, 124.9, 122.7, 120.3, 119.8, 77.3, 63.0 (d, J = 5.0 Hz), 16.1 (d, J = 6.0 Hz); 31P NMR (162 MHz CDCl3): δ 4.04; Anal. Calcd for C17H18ClN2O3P: C, 55.98; H, 4.97; N, 7.68%. Found: C, 56.16; H, 5.02; N, 7.79%. Diethyl(5-methoxy-2-(4-methoxyphenyl)-2H-indazol3-yl)phosphonate (3oa). Light yellow liquid (83%, 64.74 mg); Rf = 0.45 (PE/EA = 65:35); 1H NMR (400 MHz, CDCl3): δ 7.71 (dd, J = 9.6 Hz, 2.4 Hz 1H), 7.57−7.53 (m, 2H), 7.34 (d, J = 2.4 Hz, 1H), 7.07 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 7.01−6.97 (m, 2H), 4.13−4.02 (m, 4H), 4.00−3.96 (m, 9053

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

3H), 3.95−3.87 (m, 3H), 1.20 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.2, 157.2, 145.4 (d, J = 16.0 Hz), 134.2, 129.5 (d, J = 19.0 Hz), 127.5, 122.7 (d, J = 15.0 Hz), 121.0, 119.5, 113.8, 97.4, 77.3, 62.6 (d, J = 6.0 Hz), 55.6 (d, J = 10.0 Hz), 16.2 (d, J = 16.0 Hz); 31P NMR (162 MHz CDCl3): δ 5.62; Anal. Calcd for C19H23N2O5P: C, 58.46; H, 5.94; N, 7.18%. Found: C, 58.26; H, 6.01; N, 7.27%. Diethyl(5-methoxy-2-(p-tolyl)-2H-indazol-3-yl)phosphonate (3pa). Brown gummy mass (86%, 64.32 mg); Rf = 0.45 (PE/EA = 65:35); 1H NMR (400 MHz, CDCl3): δ 7.71 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 7.53−7.50 (m, 2H), 7.35 (d, J = 2.4 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.06 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 4.12−3.93 (m, 4H), 3.89 (s, 3H), 2.43 (s, 3H), 1.18 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.1, 145.4 (d, J = 16.0 Hz), 139.4, 138.6, 129.6 (d, J = 18.0 Hz), 129.2, 126.0, 123.1, 122.1, 120.9, 119.5, 97.4, 62.6 (d, J = 6.0 Hz), 55.5, 21.3, 16.1 (d, J = 7.0 Hz); 31P NMR (162 MHz CDCl3): δ 5.54; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C19H23N2O4PNa, 397.12876; found, 397.1287. Dimethyl(2-phenyl-2H-indazol-3-yl)phosphonate (3ab). Yellow liquid (81%, 48.92 mg); Rf = 0.50 (PE/EA = 70:30); 1H NMR (400 MHz, CDCl3): δ 8.07−8.05 (m, 1H), 7.88−7.85 (m, 1H), 7.68−7.65 (m, 2H), 7.55−7.51 (m, 3H), 7.43−7.39 (m, 1H), 7.32−7.29 (m, 1H), 3.69 (s, 3H), 3.66 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.8 (d, J = 16.0 Hz), 140.8, 129.8, 128.9, 128.5 (d, J = 5.0 Hz), 128.4, 127.1, 126.3, 125.0, 121.1, 118.4, 53.2 (d, J = 5.0 Hz); 31P NMR (162 MHz CDCl3): δ 7.74; Anal. Calcd for C15H15N2O3P: C, 59.60; H, 5.00; N, 9.27%. Found: C, 59.38; H, 5.03; N, 9.32%. Dimethyl(2-(p-tolyl)-2H-indazol-3-yl)phosphonate (3bb). Off white solid (84%, 53.08 mg); Rf = 0.45 (PE/EA = 80:20); mp 82−83 °C; 1H NMR (400 MHz, CDCl3): δ 8.06− 8.04 (m, 1H), 7.87−7.84 (m, 1H), 7.55−7.51 (m, 2H), 7.42− 7.38 (m, 1H), 7.33−7.27 (m, 3H), 3.69 (s, 3H), 3.66 (s, 3H), 2.45 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.6 (d, J = 16.0 Hz), 139.7, 138.3, 129.3, 128.3 (d, J = 17.0 Hz), 126.9, 125.9, 124.8, 123.5, 121.2 (d, J = 32.0 Hz), 118.3, 53.0 (d, J = 6.0 Hz), 21.3; 31P NMR (162 MHz CDCl3): δ 7.93; Anal. Calcd for C16H17N2O3P: C, 60.76; H, 5.42; N, 8.86%. Found: C, 60.62; H, 5.37; N, 8.77%. Diisopropyl(2-(p-tolyl)-2H-indazol-3-yl)phosphonate (3bc). Yellow gummy mass (85%, 63.24 mg); Rf = 0.50 (PE/ EA = 75:25); 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.4 Hz, 1H), 7.84−7.81 (m, 1H), 7.58−7.54 (m, 2H), 7.39−7.35 (m, 1H), 7.30−7.24 (m, 3H), 4.74−4.62 (m, 2H), 2.44 (s, 3H), 1.25 (d, J = 6.0 Hz, 6H), 1.14 (d, J = 6.0 Hz, 6H); 13 C{1H} NMR (100 MHz, CDCl3): δ 148.6 (d, J = 16.0 Hz), 139.5, 138.8, 129.2, 128.3 (d, J = 20.0 Hz), 126.9, 126.4, 124.3, 124.0, 121.9, 118.1, 72.1 (d, J = 6.0 Hz), 24.0 (d, J = 4.0 Hz), 23.8 (d, J = 4.0 Hz), 21.3; 31P NMR (162 MHz CDCl3): δ 2.30; Anal. Calcd for C20H25N2O3P: C, 64.51; H, 6.77; N, 7.52%. Found: C, 64.72; H, 6.73; N, 7.43%. Diisopropyl(5-fluoro-2-phenyl-2H-indazol-3-yl)phosphonate (3mc). Yellow liquid (80%, 60.16 mg); Rf = 0.55 (PE/EA = 80:20); 1H NMR (400 MHz, CDCl3): δ 7.82− 7.79 (m, 2H), 7.69−7.66 (m, 2H), 7.51−7.50 (m, 3H), 7.21− 7.16 (m, 1H), 4.71−4.63 (m, 2H), 1.23 (d, J = 6.4 Hz, 6H), 1.13 (d, J = 6.4 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.8 (d, J = 242.0 Hz), 146.1 (d, J = 16.0 Hz), 141.1, 129.5, 128.7, 126.4, 120.3 (d, J = 10.0 Hz), 119.6, 118.9, 118.6, 104.7 (d, J = 26.0 Hz), 72.2 (d, J = 6.0 Hz), 23.9 (d, J = 5.0 Hz), 23.8 (d, J = 4.0 Hz); 31P NMR (162 MHz CDCl3): δ 1.87; Anal.

Calcd for C19H22FN2O3P: C, 60.63; H, 5.89; N, 7.44%. Found: C, 60.47; H, 5.96; N, 7.50%.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b01121. Scanned copies of 1H, 13C{1H}, and 31P NMR spectra of the synthesized compounds (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Susmita Mondal: 0000-0002-8795-942X Alakananda Hajra: 0000-0001-6141-0343 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS A.H. acknowledges the financial support from SERB-DST (grant no. EMR/2016/001643). P.G. thanks UGC-New Delhi (UGC−JRF) and S.M. thanks CSIR-New Delhi (CSIR−SRF) for their fellowships.

■

REFERENCES

(1) (a) Hérault, D.; Nguyen, D. H.; Nuel, D.; Buono, G. Reduction of Secondary and Tertiary Phosphine Oxides to Phosphines. Chem. Soc. Rev. 2015, 44, 2508−2528. (b) Li, Y.; Lu, L.-Q.; Das, S.; Pisiewicz, S.; Junge, K.; Beller, M. Highly Chemoselective Metal-Free Reduction of Phosphine Oxides to Phosphines. J. Am. Chem. Soc. 2012, 134, 18325−18329. (2) Queffélec, C.; Petit, M.; Janvier, P.; Knight, D. A.; Bujoli, B. Surface Modification Using Phosphonic Acids and Esters. Chem. Rev. 2012, 112, 3777−3807. (3) (a) Sawa, M.; Kiyoi, T.; Kurokawa, K.; Kumihara, H.; Yamamoto, M.; Miyasaka, T.; Ito, Y.; Hirayama, R.; Inoue, T.; Kirii, Y.; Nishiwaki, E.; Ohmoto, H.; Maeda, Y.; Ishibushi, E.; Inoue, Y.; Yoshino, K.; Kondo, H. New Type of Metalloproteinase Inhibitor: Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids. J. Med. Chem. 2002, 45, 919−929. (b) Lassaux, P.; Hamel, M.; Gulea, M.; Delbrück, H.; Mercuri, P. S.; Horsfall, L.; Dehareng, D.; Kupper, M.; Frère, J.-M.; Hoffmann, K.; Galleni, M.; Bebrone, C. Mercaptophosphonate Compounds as Broad-Spectrum Inhibitors of the Metallo-Beta-Lactamases. J. Med. Chem. 2010, 53, 4862−4876. (4) Jiménez, A. M.; Navas, M. J. Chemiluminescent Methods in Agrochemical Analysis. Crit. Rev. Anal. Chem. 1997, 27, 291−305. (5) Weber, L. Recent Developments in the Chemistry of Metallophosphaalkenes. Coord. Chem. Rev. 2005, 249, 741−763. (6) (a) Yamashita, J.; Suyama, T.; Asai, K.; Yamada, M.; Niimi, T.; Fujie, M.; Nakamura, S.; Ohnishi, K.; Yamashita, M. Research and Development of Phospha Sugar Anti-cancer Agents with Antileukemic Activity. Heterocycl. Commun. 2010, 16, 89−97. (b) Monge, S.; Canniccioni, B.; Graillot, A.; Robin, J.-J. Phosphorus-Containing Polymers: A Great Opportunity for the Biomedical Field. Biomacromolecules 2011, 12, 1973−1982. (7) Demkowicz, S.; Rachon, J.; Daśko, M.; Kozak, W. Selected Organophosphorus Compounds with Biological Activity. Applications in Medicine. RSC Adv. 2016, 6, 7101−7112. (8) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. A Novel Synthesis of Dialkyl Arenephosphonates. Synthesis 1981, 1981, 56− 57. (9) (a) Baillie, C.; Xiao, J. Catalytic Synthesis of Phosphines and Related Compounds. Curr. Org. Chem. 2003, 7, 477−514. 9054

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055

ACS Omega

Article

(b) Oestreich, M.; Tappe, F.; Trepohl, V. Transition-Metal-Catalyzed C-P Cross-Coupling Reactions. Synthesis 2010, 2010, 3037−3062. (c) Demmer, C. S.; Krogsgaard-Larsen, N.; Bunch, L. Review on Modern Advances of Chemical Methods for the Introduction of a Phosphonic Acid Group. Chem. Rev. 2011, 111, 7981−8006. (d) Hu, J.; Zhao, N.; Yang, B.; Wang, G.; Guo, L.-N.; Liang, Y.-M.; Yang, S.-D. Copper-catalyzed C−P Coupling through Decarboxylation. Chem. Eur. J. 2011, 17, 5516−5521. (e) Feng, C.-G.; Ye, M.; Xiao, K.-J.; Li, S.; Yu, J.-Q. Pd(II)-Catalyzed Phosphorylation of Aryl C−H Bonds. J. Am. Chem. Soc. 2013, 135, 9322−9325. (f) Gelman, D.; Jiang, L.; Buchwald, S. L. Copper-Catalyzed C−P Bond Construction via Direct Coupling of Secondary Phosphines and Phosphites with Aryl and Vinyl Halides. Org. Lett. 2003, 5, 2315−2318. (g) Ranu, B. C.; Samanta, S.; Hajra, A. Indium−Mediated Allylation of β-Keto Phosphonates. J. Org. Chem. 2001, 66, 7519−7521. (10) Malamas, M. S.; Millen, J. Quinazolineacetic Acids and Related Analogs as Aldose Reductase Inhibitors. J. Med. Chem. 1991, 34, 1492−1503. (11) (a) Qian, S.; Cao, J.; Yan, Y.; Sun, M.; Zhu, H.; Hu, Y.; He, Q.; Yang, B. SMT-A07, A 3-(Indol-2-yl) Indazole Derivative, Induces Apoptosis of Leukemia Cells in Vitro. Mol. Cell. Biochem. 2010, 345, 13−21. (b) Li, X.; Chu, S.; Feher, V. A.; Khalili, M.; Nie, Z.; Margosiak, S.; Nikulin, V.; Levin, J.; Sprankle, K. G.; Tedder, M. E.; Almassy, R.; Appelt, K.; Yager, K. M. Structure-Based Design, Synthesis, and Antimicrobial Activity of Indazole-Derived SAH/MTA Nucleosidase Inhibitors. J. Med. Chem. 2003, 46, 5663−5673. (c) Runti, C.; Baiocchi, L. The Chemistry of Benzydamine. Int. J. Tissue React. 1985, 7, 175−186. (d) Ikeda, Y.; Takano, N.; Matsushita, H.; Shiraki, Y.; Koide, T.; Nagashima, R.; Fujimura, Y.; Shindo, M.; Suzuki, S.; Iwasaki, T. Pharmacological Studies on a New Thymoleptic Antidepressant, 1-[3-(Dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32). Arzneim. Forsch. 1979, 29, 511− 520. (e) Lee, F.-Y.; Lien, J.-C.; Huang, L.-J.; Huang, T.-M.; Tsai, S.C.; Teng, C.-M.; Wu, C.-C.; Cheng, F.-C.; Kuo, S.-C. Synthesis of 1Benzyl-3-(5’-hydroxymethyl-2’-furyl)indazole Analogues as Novel Antiplatelet Agents. J. Med. Chem. 2001, 44, 3746−3749. (f) Lena, M. D.; Lorusso, V.; Latorre, A. Paclitaxel, Cisplatin and Lonidamine in Advanced Ovarian Cancer. A phase II Study. Eur. J. Cancer 2001, 37, 364−368. (g) Han, W.; Pelletier, J. C.; Hodge, C. N. Tricyclic ureas: A New Class of HIV-1 Protease Inhibitors. Bioorg. Med. Chem. Lett. 1998, 8, 3615−3620. (h) Cross, J. B.; Zhang, J.; Yang, Q.; Mesleh, M. F.; Romero, J. A. C.; Wang, B.; Bevan, D.; Poutsiaka, K. M.; Epie, F.; Moy, T.; Daniel, A.; Shotwell, J.; Chamberlain, B.; Carter, N.; Andersen, O.; Barker, J.; Ryan, M. D.; Metcalf, C. A.; Silverman, J.; Nguyen, K.; Lippa, B.; Dolle, R. E. Discovery of Pyrazolopyridones as a Novel Class of Gyrase β Inhibitors Using Structure Guided Design. ACS Med. Chem. Lett. 2016, 7, 374−378. (12) (a) Chung, C. K.; Bulger, P. G.; Kosjek, B.; Belyk, K. M.; Rivera, N.; Scott, M. E.; Humphrey, G. R.; Limanto, J.; Bachert, D. C.; Emerson, K. M. Process Development of C−N Cross-Coupling and Enantioselective Biocatalytic Reactions for the Asymmetric Synthesis of Niraparib. Org. Process Res. Dev. 2014, 18, 215−227. (b) Jia, Y.; Zhang, J.; Feng, J.; Xu, F.; Pan, H.; Xu, W. Design, Synthesis and Biological Evaluation of Pazopanib Derivatives as Antitumor Agents. Chem. Biol. Drug Des. 2014, 83, 306−316. (c) Shen, H.; Gou, S.; Shen, J.; Zhu, Y.; Zhang, Y.; Chen, X. Synthesis and Biological Evaluations of Novel Bendazac Lysine Analogues as Potent Anticataract Agents. Bioorg. Med. Chem. Lett. 2010, 20, 2115−2118. (d) Veerareddy, A.; Surendrareddy, G.; Dubey, P. K. Total Syntheses of AF-2785 and Gamendazole-Experimental Male Oral Contraceptives. Synth. Commun. 2013, 43, 2236−2241. (13) (a) Halland, N.; Nazaré, M.; R’kyek, O.; Alonso, J.; Urmann, M.; Lindenschmidt, A. A General and Mild Palladium-Catalyzed Domino Reaction for the Synthesis of 2H-indazoles Angew. Angew. Chem. Int. Ed. 2009, 48, 6879−6882. (b) Shinde, A. H.; Vidyacharan, S.; Sharada, D. S. BF3·OEt2 Mediated Metal-free One-pot Sequential Multiple Annulation Cascade (SMAC) Synthesis of Complex and Diverse Tetrahydroisoquinoline Fused Hybrid Molecules. Org. Biomol. Chem. 2016, 14, 3207−3211. (c) Abed, H. B.; Weißing, N.;

Schoene, J.; Paulus, J.; Sewald, N.; Nazaré, M. Novel Strategy for the Preparation of 3-Perfluoroalkylated-2H-Indazole Derivatives. Tetrahedron Lett. 2018, 59, 1813−1815. (d) Kumar, M. R.; Park, A.; Park, N.; Lee, S. Consecutive Condensation, C-N and N-N Bond Formations: A Copper- Catalyzed One-Pot Three-Component Synthesis of 2HIndazole. Org. Lett. 2011, 13, 3542−3545. (14) (a) Naas, M.; El Kazzouli, S.; Essassi, E. M.; Bousmina, M.; Guillaumet, G. Palladium-Catalyzed Oxidative Direct C3- and C7Alkenylations of Indazoles: Application to the Synthesis of Gamendazole. Org. Lett. 2015, 17, 4320−4323. (b) Basu, K.; Poirier, M.; Ruck, R. T. Solution to the C3−Arylation of Indazoles: Development of a Scalable Method. Org. Lett. 2016, 18, 3218−3221. (c) Bogonda, G.; Kim, H. Y.; Oh, K. Direct Acyl Radical Addition to 2H-Indazoles Using Ag-Catalyzed Decarboxylative Cross-Coupling of α-Keto Acids. Org. Lett. 2018, 20, 2711−2715. (15) (a) Singsardar, M.; Dey, A.; Sarkar, R.; Hajra, A. Visible-LightInduced Organophotoredox Catalyzed Phosphonylation of 2HIndazoles with Diphenylphosphine Oxide. J. Org. Chem. 2018, 83, 12694−12701. (b) Ghosh, P.; Mondal, S.; Hajra, A. Metal-Free Trifluoromethylation of Indazoles. J. Org. Chem. 2018, 83, 13618− 13623. (c) Dey, A.; Hajra, A. Potassium Persulfate-Mediated Thiocyanation of 2H-Indazole under Iron-Catalysis. Adv. Synth. Catal. 2019, 361, 842−849. (d) Singsardar, M.; Laru, S.; Mondal, S.; Hajra, A. Visible-Light-Induced Regioselective Cross-Dehydrogenative Coupling of 2H-Indazoles with Ethers. J. Org. Chem. 2019, 84, 4543−4550. (16) (a) Liu, W.; Ackermann, L. Manganese-Catalyzed C-H Activation. ACS Catal. 2016, 6, 3743−3752. (b) Zhang, D.-L.; Li, C.-K.; Zeng, R.-S.; Shoberu, A.; Zou, J.-P. Manganese(III)-mediated Selective Phosphorylation of Enamides: Direct Synthesis of βPhosphoryl Enamides. Org. Chem. Front. 2019, 6, 236−240. (17) (a) Mu, X.-J.; Zou, J.-P.; Qian, Q.-F.; Zhang, W. Manganese(III) Acetate Promoted Regioselective Phosphonation of Heteroaryl Compounds. Org. Lett. 2006, 8, 5291−5293. (b) Wang, G.-W.; Wang, C.-Z.; Zou, J.-P. Radical Reaction of [60]Fullerene with Phosphorus Compounds Mediated by Manganese(III) Acetate. J. Org. Chem. 2011, 76, 6088−6094. (c) Ling, Z.; Peizhi, Z.; Jianfei, X.; Wangbin, S.; Jianping, Z. Manganese Acetate-Mediated Phosphorylation of Indoles. Acta Chim. Sin. 2016, 74, 811−818. (d) Yu, Y.; Yue, Z.; Ding, L.-G.; Zhou, Y.; Cao, H. Mn(OAc)3-mediated Regioselective C-H Phosphonylation of Indolizines with H-Phosphonates. ChemistrySelect 2019, 4, 1117−1120.

9055

DOI: 10.1021/acsomega.9b01121 ACS Omega 2019, 4, 9049−9055