TARIXI
lL Cloncentration able to reduce to SOc;; the rontractile response o f isolated intestine to wetylcholine. " These ronipounds were
prepared starting frorn S-methylpiperaxine by a proredure similar t o that desrribed'j5 for IJ---T-I. Yield, 48";; n1.p. 102-103" ( K t J ) ) . Anal. Calcd. for C1?H20?jd)2: C , 6i.73; H, 8.12; 11.28. Found: C, 67.92; H, 8.27; SI10.92. Yield, 68 111.p.225-228' (HCI salt) (EtOH). Anal. Calcd. for ClaH23ClS o 0 2 ;S , 9.37; C1, 11.86. Found: SI 9.02; ClI12.0B. e Yield, ,j;j( ,( ',' ., m.p. 21:3-21.5' (HC1 salt) (EtOH). -4naZ. Calcd. for C,~Ho:~C'IK202: X , 9.37; C1, 11.80. Found: S , 9.51; (:I, 11.!)1. [ol~)*fi -Lie ( c I , H20i.
by S-methylpiperazine or by 3-niethyl-3,8-diazabicyclo [3.2.1]octane, a decrease in activity was observed. ;Zs far as a comparison of the anticholinergic activity i n the tropoyl and a-methyltropoyl series is concerned, a-niethyltropoyl amides are more active than the corresponding tropoyl derivative i n the 8-methyl-3,8diazabicyclo f3.2.lIoctane series (B), but are less active in the ?;-methylpiperazine series (D). The weak anticholinergic activity of ( &)-%methyl8-a-methyltropoyl-3,8-diazabicyclo [3.2.1]octane (VI) may be correlated with the lack of structural similarity with the active isomer V. This result offers an indirect support for the assumed4pharmacological analogy of 8-methyl-3,8-diazabicyclo [X.2.1]octane (parent compound of Y)and tropane.
Acknowledgment.-The authors are grateful to 1)r. A . Wittgc'n- for her assistnncc i n revising t h e maiiiisvript .
era1 other groups bare report,ed on st)eroidal[:3,2--tI1pyrimidines. Our method for preparing the st,eroidal[X,'.'-d]pyrimidiiies employed the same intermediat#es, the 2hydroxymethylenesteroids, as used previously wit I t other steroidal licterocycles.2,5,6These intermediates were converted to the corresponding steroidal pyrimidines by the procedure of Raumgarten, ct ( I / . , ; or :I modification of t,his method. With t,his procedure, t h c pyrimidine ring was formed from the 2-hydiosymet,liylenesteroids and an amidine hydrochloride. 'I'riethylamine was generally the catalyst employed and ethanol was usually the solvent. Raumgarten, c,t nl.,? reported yields of 23-43y0 in their preparation of lionsteroidal pyrimidines. Our yields generally ran lower, hut wit11 the aid of chromatography, the steroidal pyrimidiiies could be isolated readily. 1TP-Hydroxq.-a-liydroxymethylene-:?oc-androstan-:2-0ne ( I ) and acetamidiiic hydrochloride gave 17/3-hydroxy-5a-androstano[3,2-d]2'-methylpyrimidine (2). ..I side product \vas isolated from the acid-soluble part of the reaction mixture and shown t o he 2-aminomethylene-17p-hydroxy-3oc-~ntlrostan-3-one (3). Similarly, when l~~-liydroxy-%-liydroxymethyle~i~~17P-methyl-5cr-androstan-3-one (4) was treated wit11 acetamidine and formamidine hydrochlorides, the, pyrimidines 5 and 6, respectively, were obtained. TI](> enamine 7 was isolated from the reaction mixt,ure fro111 (1) Paper I X : P . E:. Stiaw, 1.: JV. ( : \ , l i t i . IC. P. .lenriin Clarke, in press. (2) R. 0. Clinton, A. J . Manson, I:. LV. Stonner, A. I,. Beyler, ( i . 0. I ' u t t H , and A. Arnold, .I. A m . Ciiem. Soc., 81, 1.513 (l!J59). ( 3 ) H. .Intaki and Y. Petrow, J . Chem. Soc., 301 (1951!, have r e p o r t e d l',f~',11'-triazafluoreno(3',2': 2,3)cholestane. (4) (a) T. Colton a n d I. Loas, U. S. Pateut 2,9YY,O92 (Septe~ober5 . 2 U t ; l I : (b) J. Zderic, R . Halpern, €I. Carpio, .\. Riiiz, D. Limon, 1,. Magana, l r . JimBnez, A. Bowers, and FL. Ringold. Chem. I n d . (London), 1623 ( 1 W O ) : (c) P. Ruggeri, C . Gandolfi, and 1). Chiaramonti, Gam. C h i m Ital., 92, 7 6 8
hlanson. 1:. kV, Stonner, t l . C', Neurnann, li. C;. Cliristianst~n, R . L. Clarke, ,J. H. Ackerinan. 1). 1:. Page, . I . u'. I)ean, T). l
