1,2-diphenyldiselane -Drug Synthesis Database

【结构式】

【分子编号】39170

【品名】1,2-diphenyldiselane

【CA登记号】1666-13-3

【分子式】C₁₂H₁₀Se₂

【分子量】312.1314

【元素组成】C 46.18% H 3.23% Se 50.59%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(A)

The Wittig reaction of 1alpha-acetoxy-2alpha-(6-methoxycarbonyl-hex-2-cis-enyl)-3beta-formyl-4alpha-(2-tetrahydropyranyloxy)cyclopentane (I) and dimethyl 2-oxo-3-(3-trifluoromethylphenoxy)propylphosphonate (II) by means of NaH in hot THF gives 9alpha-acetoxy-11alpha-(2-tetrahydropyranyloxy)-15-oxo-16-(3-trifluoromethylphenoxy)-17,18,19,20-tetranorprosta-5-cis-13-trans-dienoate (III), which is reduced with NaBH4 in methanol yielding the protected trihydroxy compound (IV). The partial hydrolysis of (IV) with K2CO3 in methanol affords the dihydroxytetrahydropyranyloxy compound (V), which by reaction with diphenyldiselenide (A) by means of 17-butyllithium and diisopropylamine in THF is converted into the mixed selenide (VI). The treatment of (VI) with H2O2 in THF-ethyl acetate gives methyl 9alpha,15alpha-dihydroxy-11alpha-(2-tetra)-17,18,19,20-tetranorprosta-2-trans-5-cis-13-trans-trienoate (VII), which is finally treated with HCl in THF-water to eliminate the tetrahydropyranyl group.

参考文献中间体

合成目标

【1】 Hayashi, M.; et al.; US 4065632 .
【2】 Castaner, J.; Riberos, J.; ONO-995. Drugs Fut 1980, 5, 10, 499.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	39170	1,2-diphenyldiselane	1666-13-3	C₁₂H₁₀Se₂	详情	详情
(I)	20983	methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-formyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate		C₂₂H₃₄O₇	详情	详情
(II)	32121	dimethyl 2-oxo-3-[3-(trifluoromethyl)phenoxy]propylphosphonate		C₁₂H₁₄F₃O₅P	详情	详情
(III)	39167	methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E)-3-oxo-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate		C₃₂H₄₁F₃O₈	详情	详情
(IV)	39168	methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate		C₃₂H₄₃F₃O₈	详情	详情
(V)	39169	methyl (Z)-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate		C₃₀H₄₁F₃O₇	详情	详情
(VI)	39171	methyl (Z)-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-2-(phenylselanyl)-5-heptenoate		C₃₆H₄₅F₃O₇Se	详情	详情
(VII)	39172	methyl (2E,5Z)-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-2,5-heptadienoate		C₃₀H₃₉F₃O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The reaction of sec-butyl crotonate (I) with butylmagnesium bromide (II) by means of Cu2Cl2 in refluxing ether gives sec-butyl 3-methylheptanoate (III), wich is condensed with dimethyl methylphosphonate (IV) by means of butyllithium in THF at -70 C to afford dimethyl 2-oxo-4-methylphosphonate (V). The Wittig condensation of (V) with 1alpha-acetoxy-2alpha-(6-methoxycarbonylhexyl)-3beta-formyl-4alpha(tetrahydropyranyloxy)cyclopentane (VI) by means of NaH inTHF yields methyl 9alpha-acetoxy-11alpha-(tetrahydropyranyloxy)-15-oxo-17,20-dimethylprost-trans-13-enoate (VII), which is reduced with NaBH4 in methanol to the 15-hydroxy compound (VIII). Selective hydrolysis of (VIII) with p-toluenesufonic acid in methanol gives the 11, 15-dihydroxy derivate (IX), which is then treated with dihydropyran and p-toluenesulfonic acid in methylene chloride to afford the bis-tetrahydropyranyloxy compound (X). The reactin of (X) with diphenydiselenide (XI) by means of butyllithium and diisopropylamine in THF at -70º affords the 2-phenylseleno compound (XII), which by treatment with H2O2 and NaHCO3 in ethyl acetate - THF is converted into methyl 9alpha-hidroxy-11alpha, 15lpha-bis(tetrahydropyranyloxy)-17S, 20-dimethylprosta-trans-2, trans-13-dienoate (XIII). The hydrolysis of (XIII) with KOH in ethanol gives the corresponding free acid (XIV), which is oxidized with CrO3 - H2SO4 - MnSO4 in water - ether to afford 9-oxo-11alpha, 15alpha-bis(tetrahydropyranyloxy)-17S, 20-dimethylprosta-trans-2, trans-13-dienoic acid (XV). Finally this compound is deprotected by treatment with hot aqueous acetic acid.

参考文献中间体

合成目标

【1】 Hayashi, M.; Kori, S. Kori, S.; Ohyama, I.; Iguchi, S.; Okada, T. (Ono Pharmaceutical Co., Ltd.); GB 1545213 .
【2】 Hayashi, M.; Iguchi, S.; Okada, T. (Ono Pharmaceutical Co., Ltd.); DE 3002677 DE 3002677; FR 2447375; GB 2041368; JP 80100360 .
【3】 Castaner, J.; Hillier, K.; Ono-1206. Drugs Fut 1982, 7, 2, 116.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	59729	sec-butyl (E)-2-butenoate		C₈H₁₄O₂	详情	详情
(II)	42802	bromo(butyl)magnesium	693-03-8	C₄H₉BrMg	详情	详情
(III)	59730	sec-butyl 3-methylheptanoate		C₁₂H₂₄O₂	详情	详情
(IV)	13607	dimethyl methylphosphonate	756-79-6	C₃H₉O₃P	详情	详情
(V)	59733			C₁₁H₂₃O₄P	详情	详情
(VI)	59732	methyl 7-{(1R)-5-(acetyloxy)-2-formyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}heptanoate		C₂₂H₃₆O₇	详情	详情
(VII)	59731	methyl 7-{(1R)-5-(acetyloxy)-2-[(E)-5-methyl-3-oxo-1-nonenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}heptanoate		C₃₁H₅₂O₇	详情	详情
(VIII)	59734	methyl 7-{(1R)-5-(acetyloxy)-2-[(E,3S)-3-hydroxy-5-methyl-1-nonenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}heptanoate		C₃₁H₅₄O₇	详情	详情
(IX)	59735	methyl 7-{(1R)-5-(acetyloxy)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-methyl-1-nonenyl]cyclopentyl}heptanoate		C₂₅H₄₄O₆	详情	详情
(X)	59736	methyl 7-{(1R)-5-(acetyloxy)-2-{(E,3S)-5-methyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-nonenyl}-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}heptanoate		C₃₇H₆₄O₈	详情	详情
(XI)	39170	1,2-diphenyldiselane	1666-13-3	C₁₂H₁₀Se₂	详情	详情
(XII)	59737	methyl 7-{(1R)-5-(acetyloxy)-2-{(E,3S)-5-methyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-nonenyl}-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}-2-(phenylselanyl)heptanoate		C₄₃H₆₈O₈Se	详情	详情
(XIII)	59738	methyl (E)-7-{(1R)-5-hydroxy-2-{(E,3S)-5-methyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-nonenyl}-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}-2-heptenoate		C₃₅H₆₀O₇	详情	详情
(XIV)	59739	(E)-7-{(1R)-5-hydroxy-2-{(E,3S)-5-methyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-nonenyl}-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}-2-heptenoic acid		C₃₄H₅₈O₇	详情	详情
(XV)	59740	(E)-7-{(1R)-2-{(E,3S)-5-methyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-nonenyl}-5-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl}-2-heptenoic acid		C₃₄H₅₆O₇	详情	详情

Extended Information