Heterocyclic Steroids i n the Antiinflammatory Series'
)H
Rr,
h
I
il
lteiuoval of thc 2'-niercapto group could he carriccl out by iiitric acid oxidation, or better with alkaliiicb hydrogen peroxide and subsequelit acidification of tliv sulfinic arid sodium salt. Reduction of tlie C-11 ketone and reilloval of tlic BJID protecting group' ' (10) J . 11. Jprague and -4, 11. Land. "Heterocyclic Coinpou~uls,"\ I J L i R. C. Elderfield, Ed.. John Wiley a n d Sons, Inc..,New York, N. Y.,19.i7. 6'.
58.1. (11) R. E. Beyler, R. 31. Aloriarty, 1:. Hoffioan, anti L. 11. S a r r t t , ./. .In'. Chrni. Sot.., 80, 1517 (19.2).
. ~ ~ T I I T F L A M M A T O R YHETEROCYCLIC STEROIDS
Septeinber, 1964
afforded 1lp, 17a,21-trihydroxy-16a-iiiethyl-20-oxo-4pregnene [3,2-d]thiazole (VI). I n order to determine if basicity is an important consideration for biological activity in the heterocyclic series, the closely related but somewhat more basic analog of the active phenylpyrazole, l l p , 17a,21trihydroxy-16 a-methyl-20-oxo-1 ’-phenyl-4-pregnen [2,3d]imidazole, was synthesized. ?;itrosation12 of the 2-formyl 3-ketone I afforded the corresponding 2-hydroxyimino 3-ketone VII. I t was planned to reduce this compound to the amino ketone with zinc in acetic acid, but isolatioii of this product could not readily be accomplished. However, reduction of the hydroxyimino ketone with zinc in acetic acid in the presence of phenylisothiocyanate afforded directly a 50% yield of the l’-phenyl-2’-niercaptoiniidazole I X (see Chart 11). Oxidative removal of the inercapto
&
585
Finally, a iiuinber of triazole derivatives mere syiithesized because of the close relation, both sterically and electronically, to the corresponding pyrazoles.I6 Reaction of the hydroxyimino ketone VI1 with hydrazine and potassiuiii hydroxide” gave 17a,20;20,21CHARTI11 VI11
BMD
XVII, R = H XVIII, R=CH20CH3
1
N-
XIV, R = 0 XV, R = Q-H,3-OH,
1
CHARTI1
I
1.
+N&,,CHs
BMD A.
XIX, R = H XX, R = CHzOCH3
HON R
’
N\N
’ VII, R = 0 VIII, R=NNHCsHs
XVI
COCHzOH - --OH “CH3
XI11
I
1
COCHzOH
BMD R ? ~ , . C H . ,
H
O
A
.H-CHp
C6Hs
XXI
bismethyleiiedioxy-l6~-niethyl-ll-oso-4-pregnene [ 3,3d]-1’,2’,3’-t’riazole(XIII) . I s The preparation of 1lp, 17a ,2 1-trihydroxy- 16aniethyl-20-oxo-2’-phenyl-4-pregneiie [3,2-d]-2’H-1’,2’,3’triazole (XVI) was carried out by coilversion of group with alkaline hydrogen peroxide and subsequent VI1 to the phenylhydrazone T’III which was acidificatioii10 led to t’he 1’-phenylimidazole X. Recyclized with phosphorus pentachloride in chlorofonnlg duction of the C-11 ketone with lithium aluiiiinuiii to 17~,20;20,21-bisiiiethyleiiedioxy-16~-i~iethyl-ll-oxohydride furnished the corresponding 110-01 XI. The 2’-phenyl-4-pregiiene [3,2-d]-2’H-l’,2’,3’-triazole (XIV) structure of X I was consistent with ultraviolet, in(see Chart 111). Subsequent reduction at C-11 and frared and nuclear magnetic r e s o n a i ~ c espectra. ~~ The hydrolysis of the bisniethyleiiedioxy protecting group latter shoiyed the C-4 proton a t T 4.05 indicat’ing that afforded XVI. the C-4,5 double bond was not attacked during t’he An attempt to cyclize T’III with copper sulfat’e course of lit,hiuiii aluiiiiiiuiii hydride reduct’ion. Reproduced a compound which had one additional atom nioval of the bisniethyleiiedioxy protecting group” of oxygen conipared to the triazole XIV. This coinafforded 1lp, 17a,21-trihydroxy-16a-iiiethyl-2O-oxo-l’- pouiid is formulated as the triazole 1’-S-oxide (XYIa). phenyl-4-pregnen [2,3-d]iiiiidazole (XII), The 3’-phenyltriazole of 6,16a-diniethy1-4,6-pregnaIn order to determine the effect of ring size on activdiene-ll~,l7a,21-triol-3,20-dione 21-acetate was preity 110,17a,2 1-trihydroxy-16a-inethyl-20-oxo-2’-phenylpared because of the remarkable potency of the cor4-pregnene [3,2-d]pyriiiiidine (XXI) was synthesized. responding 2’-pheiiylpyra~ole.~Reaction of 17a,20;Reac tioii of 17a,20 ;20,21-bisinethyleiiedioxy-2-formyl20,2 1-bismethyIenedioxy-16 a-methyl-5 a-pregnaiie16a-methyl-4-pregneii-llp-01 (XVII) wit’hben~aniidine’~ (15) This synthesis could also be carried out with the corresponding C-11 afforded 17a,20 ;20,21-bismethylenedioxy-1lp-hydroxymethoxyniethyl derivative X V I I I which is a by-product formed in t h e conversion of 16~-methylhydrocortisoneto the bismethylenedioxy derivative. 16a-methyl- 2’-pheny1-4-pregnene[3,2-d]pyrimidine T h e C-11 methoxymethyl is cleared during the hydrolysis of the bismethyl(XIX). Hydrolysis of the bisniethyleiiedioxy protecting enedioxy function. group1’ afforded the desired pyrimidine XXIlj (16) G. Nathansohn, E. Testa, and N. Di Mola [Ezperientia, 18, 57 (1962)l have reported t h e synthesis of a n u m b t r of triazolo androstanes. (Chart 111). (12)
M. Gates, J . A m . Chem. Soc., 7 2 , 228 (1950).
(13) Nuclear magnetic resonance spectra were run on a Varian 60 Mc. spectrometer a t a concentration of ca. 20 mg. in 0.3 ml. of deuteriochloro3.5 a h e r e Y is the observed band position in C.P.S. relative form. r = u / 6 0 t o benzene a s external standard. C/. G. V. D. Tiers, J . Phga. Chem., 6 2 , 1151 (1958). (14) .4. Pinner, Ber., 26, 2122 (1893).
+
(17) H. Rapoport and H. H. Chen, J . Org. Chem., 26, 313 (1960); H. Rapoport and W. Nilsson, J . A m . Chem. Soc., 83, 4262 (1961). (18) Reduction a t C-11 and hydrolysis of the B M D protecting group were carried o u t t o yield 11~.17rr,21-trihydroxy-l6a-methyl-20-oxo-~-pregnene[3,2-d]-1’,2’,3,-triazole ( X I I I a ) ; however, this compound could not be obtained crystalline. On the basis of paper strip chromatography, the sample sent for biological assay contained about 70% of X I I I a . (19) F. R. Renson and W. L. Sal-ell, Chem. Rev.,46, 1 (1950).
September, 1964
ANTIINFLAMMATORY HETEROCYCLIC STEROIDS
,587
pension was filtered, concentrated in vacuo, and taken up in afforded a sample for analysis, m.p. 248-250' dec; [ a I z 4 D +72" ( c 0.6, CHC13); Xclif:yE 248 mp ( e 11,200), 327 (13,200), ethyl acetate. The ethyl acetate solution was washed with 337 (13,600); A N " o H ; ~ ~ o H 246 mp ( e 20,000), 293 mp ( e 10,600); water and saturated NaCl solution, dried over SasS04, and conACHCI~ mal 3.0-3.2,3.7,5.88, 6.23,9.05-9.20p. centrated in vacuo to yield 5 g. of a brown oil. The greater part Anal. Calcd. for Cg5Ha1N05S~:C, 61.33; H, 6.38; N, 2.86; of the excess phenyl isothiocyanate could be removed a t 50" S, 13.10. Found: C, 61.02; H, 6.42; N,2.32; S, 12.73. in vacuo. 17a,20 ;20,21-Bismethylenedioxy-16a-methyl-ll-oxo-4- The material was adsorbed from benzene on silica gel. The pregnene[3,2-d]thiazole (IV).-A solution of 200 mg. of 111 in fractions eluted with benzene containing 2 5 4 0 % ether were 40 ml. of tetrahydrofuran was treated with 2 equiv. of sodium combined to yield 2 g. of a yellow foam. Crystallization from niethoxide. The precipitated salt was dissolved by addition of ethyl acetate afforded 1.23 g. of I X , n1.p. 240-246'. Two 40 ml. of methanol. Two equivalents of 0.1 N aqueous hydrogen further recrystallizations from methylene chlorideethyl acetate peroxide was added with stirring over a period of 5 min. and gave a sample for analysis, m.p. 291-291' (evacuated capillary); stirring was continued for an additional 90 min., followed by the [ a I z 5 D +76' ( c 0.71, CHCl,); 270 mp ( e 8750) and 321 addition of 20 ml. of 2 A- sulfuric acid. The product was isomp ( e 13,900); XCH30~%;""0H 331 mp ( e 11,500); 2.96, 3.15, lated by extraction with chloroform. Crystallization from 3.7,3.78, 5.90, 6.24, 9.1-9.2~. chloroform-ether afforded 145 mg. of IV, m.p. 295-305' dec. Anal. Calcd. for C ~ I H ~ ~ T ~C,O6~7S. S: ; H, 6.61; S,5.11; A sample for analysis after chromatography on acid washed S,6.84. Found: C, 67.96; H, 6.64; S , 5.50; S,6.14. alumina was obtained by elution with benzene-ether (19:l) and 17a,20 ;20,21-Bismethylenedioxy-l6~-methyl-ll-oxo-l Icrystallization from methylene chloride-ether, m.p. 322-325' phenyl-4-pregnen[2,3-d]imidazole (X).--4 solution consisting dec; [ a I z 4 ~ +121° ( c 0.5, CHCl,); A c t 2 271 mp ( e 8400); of 5.56 nimoles of sodium methoxide in methanol was added with A":,":" 5.88, 6.1, 6.5,9.06 p. stirring to a solution of 1.53 g. of the thiol I X (2.78 nimoles) in A n d . Calcd. for CZ5H3,NO5S:C, 65.62; H, 6.84; N, 3.06; 255 ml. of acetonitrile maintained under an atmosphere of niSI 7.00. Found: C, 64.94; H, 7.08; ru', 3.14; S, 6.95. trogen. This was followed by the addition of 5.56 mmoles of 17a,20 ;20,21-Bismethylenedioxy-11 phydroxy-16a-methy1-4hydrogen peroxide (0.1 aqueous solution) which was added pregnene[3,2-d]thiazole (V).-A suspension consisting of 125 dropwise over a period of 10 min. The solution was stirred for mg. of IV, 125 mg. of lithium aluminum hydride, and 25 ml. of 45 min. Then 125 ml. of 2 A' sulfuric acid was added with tetrahydrofuran was refluxed for 1 hr. under nitrogen, cooled in vigorous stirring. Gas evolution was observed. After 15 min. ice, and excess lithium aluminum hydride decomposed with 1.75 the product was extracted with ethyl acetate, washed x i t h ml. of water. The product was filtered, concentrated t o dryness, saturated aqueous KaHCO3 solution, followed by saturated and chromatographed on acid-washed alumina. Elution with S a C l solution, and dried over hfgsO4. Concentration to dryness benzene-ether (9:l and 3 : l ) and crystallization from etherafforded 1.5 g. of a yellow foam. Chromatography on 50 g. petroleum ether (b.p. 30-60") afforded 65 mg. of V, m.p. 217of silica gel and elut,ion with benzene-ether (1 : l), ether, and 219". Recrystallization from acetone-ether-petroleum ether ether-chloroform (19: 1) mist'ures afforded 798 mg. of crude gave a sample for analysis, m.p. 219-220"; [ a ] " D +60" ( e product.. Crystallization from met,hylene chloride-ether yielded 0.62, CHCla); 263 m p ( e 9680); Xct2 2.75, 3.0, 6.1, 520 mg. of X as yellow crystals, m.p. 222-242' dec. Further 6.5, 9.08 p. crystallization from methylene chloride-ethyl acetate and methylAnal. Calcd. for CP5HS3SO5S: C, 65.33; H, 7.24; N, 3.05; ene chloride-acetone afforded a sample for analysis, m.p. 249SI 6.98. Found: C, 65.65; H, 7.06; K,2.65; S, 6.72. 255' dec; [ a ] 2 6+113" ~ (c 0.50, CHC13'):'hC%H225 nip ( e 11~,17a,21-Trihydroxy-l6~-rnethyl-20-oxo-4-pregnene [ 3,241 17,100), 290 (9900), and 295 (10,100); : : A: 5.88, 6.21, 6.64, thiazole (VI).-A mixture of 200 mg. of V in 20 ml. of 60% 9.15, and 14.4p . aqueous formic acid was heated for 30 min. a t 100" under nitroAnal. Calcd. for C31HaBS?O3: C, 72.07: H, 7.02; S,5.42. gen. The solution was cooled with ice, extracted with chloroFound: C, 71.86; H, 6.77; N, 3.32. form, washed with aqueous sodium bicarbonate solution, and 1701,20;20,21-Bismethylenedioxy-11 P-hydroxy-l6a-methyl-1 Itaken to dryness. The white foam obtained was dissolved in phenyl-4-pregnen [2,3-d]imidazole (XI).-A suspension consisting 20 ml. of dry methanol, and 0.15 equiv. of a solution of sodium of 320 nig. of the ketone X in 55 nil. of tetrahydrofuran and 320 niethoxide in methanol was added. The solution was stirred mg. of lithium aluminum hydride was refluxed in an atmosphere for 12 min. a t room temperature under nitrogen and treated with of nitrogen for 3 hr., then cooled in ice, and excess lithium alumi1 drop of acetic acid. Most of the methanol was removed i n num hydride was destroyed with 4.0 ml. of Fater. The suspenvacuo a t a bath temperature of 35". The residue was taken up sion was filtered, and the filtrate was taken to dryness. A slightly in chloroform, washed to neutrality, and taken to dryness. yellow foam was obtained. Crystallization from acetoneCrystallization from acetone-ether afforded 75 mg. of VI, m.p. ether afforded 216 mg. of XI, m.p. 200-205". One further re131-135". Two further recrystallizations from acetone-ether crystallization from the same solvents gave a sample for analysk, and acetone-petroleum ether gave a sample for analysis, m.p. 227 mp m.p. 212-215'; [ o ] ' ~ D +55' ( e 0.54, CHC1,): XCz::H +150' ( c 0.43, CHCl,); XcEitH 263 mp 131-137'; [a]*'~ ( e 16,000), 288 (9400), and 293 (960Oi: 222 mp (€8500);Xcz23.0-3.1, 5.86, 6 . 1 5 , a n d 6 . 5 2 ~ . ( e 10,500), 278 ( l l , O O O ) , and 283 (11,300); : : : 'A 3.1-3.15, 6.23, A n d . Calcd. for CL3H31N04S:C, 6 6 . l j ; HI 7.49. Found: 6.65, and 9.1-9.3~. C, 65.97: H, 7.78. Anal. Calcd. for C31H88SP06: C, 71.79: H, 7.39; K, 5.40. 17a,20 ;20,21-Bismethylenedioxy-2-hydroxyimino-l6aFound: C, 71.68; H, 7 . 5 2 ; S , 5.52. methyl-4-pregnene-3,ll-dione(VII).-A solution of 1.0 g. of I in 6 ml. of methylene chloride, 30 ml. of glacial acetic acid, and 1lp,l7a,21-Trihydroxy-l6~~-methyl-20-oxo-l '-phenyl-42 ml. of water was cooled in ice. Sodium nitrite (158 mg.) in 7 pregnen [2,3-d]imidazole (XII).-A suspension consisting of 150 ml. of water was added with stirring, and stirring was continued mg. of the BRID XI and 15 nil. of 60Yc aqueous formic acid was for 30 min. a t 0" in a n atmosphere of nitrogen. At the end of this heated for 30 niin. a t 100" in an atmosphere of nitrogen. The time, 60 ml. of ice-water was added to the reaction mixture. The solution was cooled rapidly in ice, ice water was added, and the product was extracted with methylene chloride and washed with product was taken up in chloroform. The chloroform layer water, saturated NaHCO3, and NaCl solutions. The methylene was mashed sequentially with water, saturated NaHC03 solution, chloride solution was dried over RIgS04 and concentrated to , water, and saturated NaCl solution, dried over K a ~ S 0 4and dryness in vaczio. Cryst'allization from ethyl acetate yielded evaporated to dryness in cucuo. The crude product was dis540 mg., m.p. 240-247' dec. Several recrystallizations from solved in 100 ml. of dry methanol, 0.15 equiv. of sodium methoxide ethyl acetate afforded an analytical sample of VII, m.p. 255was added, and the solution was stirred for 15 min. a t room 257' dec; 1alZ5~ +66' ( c 0.97, CHCI,); 260 m p ( e 13,700); temperature in a nitrogen atmosphere. One drop of glacial A',"? 3.04, 5.84, 5.93, 6.14 p. acetic acid was added and the greater part of the methanol was Anal. Calcd. for C2dHalNOT: C, 64.70; H, 7.01; N, 3.14. removed in vacuo a t room temperature. The residue was taken Found: C, 64.66; H,7.20; S , 3 . 5 1 . up in ethyl acetate. The solut,ion u-as washed with saturated 17a,20 ;20,21-Bismethylenedioxy-2'-mercapto-l6a-methyl-l1- SaHCO, and NaC1 solution, dried over Na2SO4, and concenoxo-1 '-phenyl-4-pregnen [2,3-d]imidazole (IX).-Zinc dust was trated to a white glass. Crystallization from acetone afforded -added to a solution of 3.25 g. of VI1 and 3.3 ml. of phenyliso/ a nig. of XII, m.p. 1.59-177'. The mother liquor gave an thiocyanate in 65 ml. of glacial acetic acid, in ca. 100-mg. portions additional 38 mg. of compound. Recrystallization from niethevery 5-10 min. during 1 hr. with stirring. Stirring was conatid-ether, methylene chloride-acetone-ether, and methylene tinued at room temperature for an additional 3 hr. The suscBhloride-ether gave a sample for analysis, m.p. 180-184" der;
-
XCH3tt;HCL
Septeinber, 1964
A & N T I I N F L A M M A T O R YHETEROCYCLIC
STEROIDS
389
216-220'; [ ~ ] Z S D$108" ( c 0.54, acetone); ~ ' 7 258, 2 ~ 307 The cooled solution was filtered, washed with aqueous sodium bicarbonate solution, dried, and concentrated zn vucuo. Crysnip i s 40,500, 9500); XCH31:;HC1 276 mp ( E 27,400). tallization from ethyl acetate afforded 350 mg. of S X V I . A A n a l . Calcd. for C30H3&-201: C, 73.i4; H, '7.43. Found: sample for analysis was recrystallized from ethyl acetate, m.p. C, 73.63; H, 7.79. 1701,20;20,21-Bismethylenedioxy-l6or-methyl-6,1l-dioxo-3'-280-300" dec; [ C X ] * ~ D-25' ( c 1.0, CHC13); 228 mp phenyl-&-pregnane [3,2-d]-3/H-l',2',3'-triazole(XXIII).-A so(e10,600); X ~ ~ ~ ' 3 . 0 7 , 5 . 9 3 , 6 . 3 O , B . T O p . lution consisting of 2.0 g. of X X I I and 2 ml. of morpholine in 20 -4nal. Calcd. for C31H3,'?;306:C, 67.09; H, 6.81. Found: ml. of benzene was refluxed vigorously for 1 hr. in the presence C, 6'7.01; H, 7.10. of Linde molecular sieves contained in a Soxhlet extractor. The 114,17~.21-Trih~droxv-6.16~~dimethsl-20-oxo-3~-~hen~1-4,6cooled enamine TTas concentrated in vacuo, flushed once wit'h pregnadiene [3,2-d] -3'H-i/,2;,3/-triazole 21-Acetate jXXVII).A solution of 320 nig. of S X V I in 35 nil. of tetrahydrofuran benzene (infrared 5.87, 6.07, 6.16 p ) , and refluxed overnight with was stirred with 340 mg. of sodium horohydride and 3.5 nil. of 1.5 nil. of phenyl azide and 30 ml. of benzene. The solution water a t room temperature for 64 hr. The mixture was poured was concentrated in vacuo and chroniatographed on 100 g. of into aqueous NaH2P04 solution. The product was extrac,ted acid-washed alumina. Elution with chloroform and crystalwith chloroform, the est,ract was dried and concentrated in vaci~o. lization from ethyl acetate yielded 530 mg. of XXIII. A sample The crude llp-hydroxy steroid (infrared shows the absence of for analysis was crystallized from chloroform-ethyl acetate, carbonyl absorption) in 30 ml. of 6 0 5 aqueous formic acid was 228 nip ( e 10,800); m.p. 350"; [ c Y ] ~ ~+DS o ( e 1.0, CHC13); heated on the steam cone for 45 min. The cooled solution was A?': 5.90, 6.28, 6.68 p . diluted with water and extracted with chloroform. The chloroA n a l . Calrd. for C30H3&?;306: C, 67.52; H, 6.61; S,7.88. form layer was washed with water and aqueous SaHC03, dried, Found: C, 67.45: H, 6.49: ?;, 7.58. 17~u,20;20,21-Bismethylenedioxy-6p-hydroxy-6a,l6~- and concentrated in zlacuo. The product dissolved in 10 nil. of methanol WRS purged with nitrogen and allowed to stand with dimethyl-I1 -oxo-3'-phenyl-5~u-pregnane [3,2-d]-3" 1 ',2', 3'- tr iazole (XXIV).-Five milliliters of 1 S methylmagnesium iodide 0.20 ml. of 0.6 niethanolic sodium methoxide for 15 niin. at in ether was added to an azeotropically dried solution of 0.6 g. room temperature. dfter addition of a few drops of acetic acid, of X X I I I and 200 ml. of benzene at cu. 40'. The suspension was the reaction mixture was concentrated in vacuo. The residue allowed to come t o room temperature and ice-water was added was taken up in chloroform. The solution was washed with after a total reaction time of 45 min. After filtration, the water, dried, concentrated in vacuo, and acetylated with 3 ml. of benzene layer was separated, dried, and concentrated in DUCUO. acetic anhydride and 3.5 nil. of pyridine at' room temperature Crystallization from ethyl acetate-chloroform afforded 410 mg. overnight. A partition columnz8 was packed with 225 g. of of XXIV, m.p. 350-360" dec; [ C Y ] * ~ D+14" ( e 1.0, CHC13); Supercel which had been slurried with 2 1. of chloroform-isooctane X C ~ ~ 2 2 9 n i p ( ~ 1 1 , 2 0X"J0$) ; 2.9,5.92,6.29,6.67fi. (1:7 ) and 225 ml. of formamide, and washed with 3 1. of chloroA n a l . Calcd. for C3LH3&306: C, 67.74; H, i.15; ?;, '7.65. form-isooctane (1:7) saturated with formamide. The steroid Found: C, 67.54; H, 7.01; Ir;, 7.51. dispersed on 5 g. of Supercel and 5 ml. of formamide saturated 1701,20 ;20,21-Bismethylenedioxy-6,l6~-dimethyl-ll-oxo-3'- with chloroform-isooctane (1: 7 ) was poured onto the column with phenyl-5-pregnene[3,2-d] -3'H-l',2',3'-triazole (XXV).-A solu50 ml. of chloroform-isooctane (1:7), followed by 15 1. of the tion consisting of 1.2 ml. of thionyl chloride in 7 ml. of ice-cold same solvent to elute three minor components. The progress pyridine was added to 300 mg. of XXIV in 8 ml. of pyridine a t of the separation was followed by measuring the absorption 5". The solution was allowed t o come to room temperature and density a t 315 mp with a Beckman Model DU spectrophotcipoured into ice-water after a total reaction time of 35 min. The meter. Elution with 5 1. of chloroform-isooctane ( 2 :6) saturated precipitat,e was filtered and crystallized from ethyl acetate t o with forniamide folloxed by percolation of a center cut through yield 280 mg. of XXV, m.p. 245-254'; [ a ] " D f 5 " ( c 1.0: silica gel with ether afforded 65 mg. of XXVII, m.p. 204-207'. ~ H a t 224 mp ( e 11,200); 5.85, CHCl,); X C ~ ~shoulder A4sample for analysis was recrystallized from ethyl acetate6.28, 6.67 p. ether, n1.p. 204-207": [ C Y ] * ~ D+20' ( c 1.0, CHC13); XCZ:tH 263, Anal. Calcd. for C31H37?;30~: C, 70.03; H, 7.02. Found: 318 mp ( e 10,400, 22,500); ACE? 2.77, 2.95-3.00, 5.75) 5.80, C, 69.71; H, 6.80. 6.21, 6.38, 6.59 p . 17a,20 ;20,21-Bismethylenedioxy-4p-hydroxy-6,16~-dimethyl- A w l . Calcd. for C31H3,S305: C, 70.03; H, i.02. Found: 11 -oxo-3'-phenyl-5-pregnene[3,2-d] -3'H-l',2',3'-triazole (XXVI). C, 70.16; H, 7.22. -A solution of 520 mg. of XXV and 500 mg. of selenium (28) We are indebted t o R. Vitali for suggesting this partition sy-stem dioxide in 35 nil. of butanone dioxolane was refluxed for 3.5 hr.
-
Xz;:'
