1498132 Steroid [16,17-b]dioxanes E R SQUIBB & SONS Inc 15 Jan 1975 [16 Jan 1974] 1776/75 Headings C2U and C2C The invention comprises 3,20-dioxo pregnenes having an 11#-hydroxy or 11-oxo group and having at position 16,17 a fused-on 1,4-dioxane or dihydro - 1,4 - dioxin ring. Preferred are the #SP4/SP, #SP1,4/SP, #SP4,6/SP and #SP1,4,6/SP compounds of formula wherein A 1 is selected from (the valence on the left being attached to the 17-oxygen atom); R 1 is H, C 1-8 alkyl, or aryl; R 2 is H, C 1-8 alkyl or aryl-(C 1-8 alkyl); R 3 is C 1-8 alkyl, C 3-6 cycloalkyl, or aryl; R 4 and R 5 are each C 1-8 alkyl, or aryl; P is H, Me or Cl; Q is H, Me or F; X is H or halo; Y is H, YSP1/SP is OH or Y + YSP1/SP = oxo; Z is H, halo, OH or acyloxy; the term "aryl" signifying phenyl optionally sub stituted with one or more halo, C 1-8 alky or C 1-8 alkoxy groups. The inventive compounds are prepared from analogous 16,17-diol cyclic borates by synthesizing the 16,17-dioxane ring as shown in the reaction scheme infra, and subsequently optionally introducing #SP6/SP unsaturation (e.g. with DDQ) acylating at position 21 (this may also be effected on the intermediates marked * and **), hydrolysing a 21-ester group, or converting 21- OH to 21-halo via a 21-sulphonate (this may also be effected on the intermediate marked **) (R 1 , R 3 , R 4 , R 5 and Z are as above; R 6 is alkyl or aryl; R 7 is alkyl or aralkyl; each X is alkyl or the two X's together are ethylene). Reagents: (a) CH 2 :C(R 1 )N 2 ; (b) (XO) 2 C(R 4 )C(R 5 )N 2 ; (d) THP.O.CH 2 CHN 2 ; (e) m-chloroperhenzoic acid; (f) e.g. periodic acid; (g) e.g. f-toluenesulphonic acid; (h) NaBH 4 ; (i) MeSO 2 Y (Y= halo); (j) NaHCO 3 /DMSO; (k) e.g. HCl; (1) (R 3 CO) 2 O; (m) Fetizon's reagent; (n) e.g. acetic acid; (p) tautomerism. A 16,17-cycloborate is prepared from 21-chloro- 9 - fluoro - 11#,16,17 - trihydroxypregna - 1,4- diene - 3,20 - dione by reaction with boric oxide in methanol. Potassium phthalimide + - (bromomethyl) styrene # N - (2 - phenyl - 2 - propenyl)phthalimide # ethyl N - (2 - phenyl - 2 - propenyl) carbamate # ethyl N - nitroso - N - (2 - phenyl - 2- propenyl)carbamate # 2 - phenyl - 3 - diazo - 1- propene (Example 4). 2 - (Tetrahydropyran - 2 - yloxy)acetonitrile # 2 - (tetrahydropyran - 2 - yloxy)ethylamine # N - [2 - (tetrahydropyran - 2 - yloxy)ethyl]urea # N - nitroso - N - [2 - (tetrahydropyran - 2 - yloxy) ethyl]urea # 2 - (tetrahydropyran - 2 - yloxy) - 1- diazoethane (Example 18). Potassium phthalimide + -bromopropiophenone # N - (1 - methyl - 2 - oxo - 2 - phenylethyl) phthalimide # 2 - (1 - phthalimidoethyl) - 2- phenyl - 1,3 - dioxolane # 2 - (1 - aminoethyl) - 2- phenyl - 1,3 - dioxolane # 2 - phenyl - 2 - [1- (ethoxycarbonylamino)ethyl] - 1,3 - dioxolane # 2 - phenyl - 2 - (1 - diazoethyl) - 1,3 - dioxolane (Example 40). Antiinflammatory compositions for oral and topical administration comprise a compound of Formula I and a carrier.
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