Journal of Medicinal Chemistry, 1910, Vol. 13, .Yo. 6 1023
NEW C o M P o U s U s
TABLE I 1-SUBSTITUlCD DIME I'HYLPYRROLES
q-+ CHj
HiC
I
R
CH3 CHj 20-21
1-19 \0
1 2 )
4 1
0
(
S
9 10 11
12 13 14 1.i
16 17 1\
19 20
21
Starting amine K(SH!),: 2 = 1 or
1
2-hminot hiazole 2--Aminothiazoliiie 2-Aniiriobenzot hiazole 2-.~niino-5-iiitrothiazole 2--hmino-.i-(4-nitrophenyl~ulfoiiy1)thiazole 2-hmino-4-(4-bipheiiyl~-l)thiazole 2-Aminoimidazo1ea.b 2--Amino-l-niethyliniidazoleb 2- ilniirio-1,3,4-thiadiazole :j-.Aniiiio-1,2,4-triazole .j-Aminot,etrazole 2--.lmiiiopyridiiie 2-Aniiiio-3-ni tropyridiiie 2-Aniino-5-nitropgridine 2-Aminopyrimidine .j-Aminuuracil 2-Amino-4-morpholirio-s- t,riazine 3-Trifluoi,omethylaniiili1ie
CH,
Reacn time (hr)
1 ield
(XJ
Formulad
I I I I1
3
59 20 56 43
--I
CgHioXzS CgHizN26 C13141?~2s CsHgXSO2d CioHijSa03?
74-76 173-175
A B C
CiiHisK2S
121-123
D
191 .*?-194 159.5-161.3 96 (0.01) 202-203h 150-1 5 1 163- 164' 80-82 81.5-83 84-85 ( 0 . 0 2 ) j 285-288 91-92.5
E E
'i
I1
24 52 7
I1
1:i
42
I I I I
31 9 7 2
30 70 60 48 56 43 61
I I
j, .i
I1 I I1 I I
4 ..5 22 3 24 1 7 . .i
I
1.5
1-Phenyl-I -(2-pyridyl)hydrazinec 2J5-Diamiiio-1,3,4-t,hiadiazole 2,6-L)iaminopyridiiie
.-I
Product
Reerystnm solvent
Prep method
cI .)
5 .i 70 2.5 33
CiaHi2FaN
bp (mm) or mp,
O C
78 (0.025p
f X1-82.30
F C A G G H (95 : 5 ) G
30-32k
H (7: 1 a t
64.5-66.5
-78') H (1:1)
122-1 24 152-156
'
I I
Sulfate. Prepared Prepared accordirig t'o A . G . Beaman, R. Duschinsky, aiid W. P. Tautz, U. S. Patent 3,287,468 (1966). according to G . Palazzo aiid L. Baiocchi [ A n n . Chim. (Rome), 55, 935 (1965)]. d Compounds (excluding 3, 10, 21) were analyzed for C, H, N and, where applicable, C1, F, S. A11 values were within +0.4% of theoretical. e N. P. Buu-Hoi [ J .Chem. Soc., 2882 (194911 reported bp 130-132" (13 mm). f Unstable to distillation; purified by preparative glpc. 0 W. S. Bishop [ J . Amer. Chem. Soc., 67, 2261 (1945)] report'ed mp 79-79.?". R. Rips, C. Derappe, and X. P. Buu-Hal [ J . Org. Chum., 25, 390 (1960)l reported mp 203". XIp 127", footnot,e h . 2 K.P. Buu-Hol and N. D. Xuong [ibid., 28, 850 (1955)l bp 150-151O (12 mm). k H. Gilman, C. G. Stucknisch, and J. F. Sobia [ J . Amer. Chem. SOC.,68, 326 (1946)l reported mp 42'. 2 N. P. Buu-HoI, R.Rips, and C. Derappe [Bull. SOC.Chim. Fr., 3456 (1965)l reported mp 135'. A, i-PrOH; B, Et'sO-hexane (1: 1); C, C6H6; D, hexane; E, AIezCO; F, CHCla; (+,petroleum ether (bp 90-100'); H, EtOH-H20; I, Et2O. I
and in vivo anthelmintic tests. biological activity.
S o n e showed significant
Experimental Section XIelting points were taken in open capillary tubes with a calibrated thermometer using a Thomas-Hoover melting point apparatus. The ir and nmr spectra of each compound were consistent with the expected structure. Elemental analyses were performed by Spang Microanalytical Laboratory, .4nn Arbor, blich. Solvents were removed under vacuum on a rotary evaporator. Analytical glpc determinations were carried out with an F & R I Model 500 gas chromatograph equipped with a llodel 1609 flame ionizatioii dectector. The stainless steel coliimii uaed was 0 . 6 Z X 120 L" packed with 35% SE-30 silicone giini rribber on acid-washed, base-washed, and silanized Anakrom solid support. Preparative glpc separations were accomplished with an F & ?\I Model 776 Prepmaster J r . using N Bas the carrier gas. The A1 column used was 2.5 X 200 em and was packed with the same material described above. Unless otherwise indicated, the amines were commercially available. Compounds Were Prepared by One of Two Methods. Method I.-->Aii equivaleiit amount of' amiiie hydroohloride aiid 2,5-
hexanedioiie were refluxed in DMF until glpc analysis showed the disappearance of the dione peak. I n most cases HBOformed during the reaction was removed by using a Dean-Stark water separator filled with molecular sieves. After completion of the reaction, the D N F was poured into a large volume of H20 and the product was extracted (EtzO). The ether was dried (MgSOA) and evaporated to give a crude product which was purified by recrystallization or dist,illation. Method 11.-An equivalent amount of amine (free base) a i d 2,5-hexanedione were refluxed in an aromatic organic solvent (C6H6 or C s H j a k ) containing a catalytic amount of p-toluenesulfonic acid (pTsA). The progress of the reaction was followed by the amount of Hi0 which collected in a Dean-Stark water separator, or by glpc analysis. After t,he reaction was complete, the pTsA was removed by extraction with aq NaHCO, solutioii and the solvent was dried (MgSOd) and evaporated. The crude product was purified by recryst,allizatiori or distillation.
Acknowledgments.-The aut'hors nish to thank Dr. W. E. lleredit'h, N r . C. A. Johnson, and l I r . J. W. Wallace for biological screening, and Dr. P. &I. Weiritraub For preparing the 1-phenyl-1-(Bpyridy1)hl-draziiie used to synthesize 19.
