bromo(2-propynyl)magnesium -Drug Synthesis Database

【结构式】

【分子编号】29064

【品名】bromo(2-propynyl)magnesium

【CA登记号】

【分子式】C₃H₃BrMg

【分子量】143.26582

【元素组成】C 25.15% H 2.11% Br 55.77% Mg 16.96%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIV)

The oxidation of 1-hepten-3-ol (XII) with pyridinium chlorochromate gives 1-hepten-3-one (XIII), which by a Grignard condensation with propargylmagnesium bromide (XIV) is converted into 4-hydroxy-4-vinyl-1-octyne (XV). The protection of (XV) with trimethylsilyl chloride and imidazole in DMF yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XVI), which by reaction with tri-n-butyl-stannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVII). Finally, this compound by reaction with butyllithium and copper -1-pentyne-tributylphosphine (C) in HMPT yields the copper salt (VIII), already obtained.

参考文献中间体

合成目标

【1】 Grudzinkas, C.V.; Bimbaum, J.E.; Chen. S.L.; Chan, P.S.; Floyd, M.B.; Weiss, M.J.; Cervoni, P.; Prostaglandins and congeners. 29. (16RS)-Rac-15-deoxy-16-hydroxy-16-vivyl-protaglandin E2, an orally and transdermally active hypotensive agent of prolonged duration. J Med Chem 1982, 25, 5, 492-494.
【2】 Hillier, K.; Blancafort, P.; Serradell, M.N.; Castaner, J.; CL-115,347. Drugs Fut 1983, 8, 4, 307.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	36021	[(1E)-4-butyl-4-[(trimethylsilyl)oxy]-1,5-hexadienyl](1-pentynyl)copper		C₁₈H₃₂CuOSi	详情	详情
(XII)	36025	1-hepten-3-ol	4938-52-7	C₇H₁₄O	详情	详情
(XIII)	36026	1-hepten-3-one		C₇H₁₂O	详情	详情
(XIV)	29064	bromo(2-propynyl)magnesium		C₃H₃BrMg	详情	详情
(XV)	29325	3-butyl-1-hexen-5-yn-3-ol		C₁₀H₁₆O	详情	详情
(XVI)	36027	1-butyl-1-vinyl-3-butynyl trimethylsilyl ether; [(1-butyl-1-vinyl-3-butynyl)oxy](trimethyl)silane		C₁₃H₂₄OSi	详情	详情
(XVII)	36028	(E)-1-butyl-4-(tributylstannyl)-1-vinyl-3-butenyl trimethylsilyl ether; [[(E)-1-butyl-4-(tributylstannyl)-1-vinyl-3-butenyl]oxy](trimethyl)silane		C₂₅H₅₂OSiSn	详情	详情
(C)	29069	1-pentynylcopper		C₅H₇Cu	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The Grignard reaction of propargylmagnesium bromide (I) with 2-hexanone (II) in ether gives 4-methyloct-1-in-4-ol (III), which by reaction with diisobutylaluminum hydride and I2 is converted to 1-iodo-4-methyloct-1-en-4-ol (IV). The reaction of (IV) with dihydropyran and p-toluenesulfonic acid yields the corresponding tetrahydropyranyloxy derivative (V), which by reaction with tert-butyllithium and copper pentyne (VI) affords the corresponding organolithiocuprate (VII). The condensation of (VII) with 4R-(tetrahydropyranyloxy)-2-[7-(tetrahydropyranyloxyl)heptyl]cyclopent-2-en-1-one (VIII) in ether gives 1,11,16-tris(tetrahydropyranyloxy)-16-methylprost-13-en-9-one (IX), which is finally deprotected by a treatment with acetic acid in water THF.

参考文献中间体

合成目标

【1】 Woessner, W.D.; Biddlecom, W.G.; Kluender, H.C. (Bayer Corp.); Preparation of 15-deoxy-16-hydroxyprostaglandins. US 4132738 .
【2】 Castaner, J.; Serradell, M.N.; Rioprostil. Drugs Fut 1985, 10, 3, 207.

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)	29064	bromo(2-propynyl)magnesium		C₃H₃BrMg	详情	详情
(II)	29065	2-hexanone	591-78-6	C₆H₁₂O	详情	详情
(III)	29066	4-methyl-1-octyn-4-ol		C₉H₁₆O	详情	详情
(IV)	29067	(E)-1-iodo-4-methyl-1-octen-4-ol		C₉H₁₇IO	详情	详情
(V)	29068	(E)-2-butyl-5-iodo-2-methyl-4-pentenyl tetrahydro-2H-pyran-2-yl ether		C₁₅H₂₇IO₂	详情	详情
(VI)	29069	1-pentynylcopper		C₅H₇Cu	详情	详情
(VIII)	29070	(4R)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[8-(tetrahydro-2H-pyran-2-yloxy)octyl]-2-cyclopenten-1-one		C₂₄H₄₀O₅	详情	详情
(IX)	29071	(2R,3S,4R)-3-[(E)-4-methyl-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-octenyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-[8-(tetrahydro-2H-pyran-2-yloxy)octyl]cyclopentanone		C₃₉H₆₈O₇	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIII)

The oxidation of 1-hepten-3-ol (XI) with pyridinium chlorochromate gives 1-hepten-3-one (XIII), which by a Grignard condensation with propargylmagnesium bromide (XIII) is converted to 4-hydroxy-4-vinyl-1-octyne (XIV). The protection of (XIV) with trimethylsilyl chloride and imidazole as before yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XV), which by reaction with tri-n-butylstannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVI). Finally, this compound, by reaction with butyllithium and copper(I)-1-pentyne tributylphosphine as before yields the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trime-thylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X). Finally, this compound is hydrolyzed with acetic acid in THF water.

参考文献中间体

合成目标

【1】 Grudzinkas, C.V.; Bimbaum, J.E.; Chen. S.L.; Chan, P.S.; Floyd, M.B.; Weiss, M.J.; Cervoni, P.; Prostaglandins and congeners. 29. (16RS)-Rac-15-deoxy-16-hydroxy-16-vivyl-protaglandin E2, an orally and transdermally active hypotensive agent of prolonged duration. J Med Chem 1982, 25, 5, 492-494.
【2】 Adaikan, P.G.; Serradell, M.N.; Castaner, J.; DHV-PGE2. Drugs Fut 1985, 10, 5, 382.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	29319	1-Pentynyl copper salt tri(tert-butyl)phosphine complex		C₁₇H₃₄CuP	详情	详情
(VIII)	29320	[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl](1-pentynyl)copper		C₁₉H₃₄CuSi	详情	详情
(IX)	29321	(4R)-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]-2-cyclopenten-1-one		C₂₀H₃₆O₂Si₂	详情	详情
(X)	29322	(2R,3R,4R)-3-[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl]-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]cyclopentanone		C₃₄H₆₄O₂Si₃	详情	详情
(XI)	29323	1-hexen-3-ol	4798-44-1	C₆H₁₂O	详情	详情
(XII)	29324	1-hexen-3-one	1629-60-3	C₆H₁₀O	详情	详情
(XIII)	29064	bromo(2-propynyl)magnesium		C₃H₃BrMg	详情	详情
(XIV)	29325	3-butyl-1-hexen-5-yn-3-ol		C₁₀H₁₆O	详情	详情
(XV)	29326	(2-butyl-2-vinyl-4-pentynyl)(trimethyl)silane		C₁₄H₂₆Si	详情	详情
(XVI)	29327	[(E)-2-butyl-5-(tributylstannyl)-2-vinyl-4-pentenyl](trimethyl)silane		C₂₆H₅₄SiSn	详情	详情

Extended Information