bis(1,2-dimethylpropyl)borane -Drug Synthesis Database

【结构式】

【分子编号】20452

【品名】bis(1,2-dimethylpropyl)borane

【CA登记号】132509-17-2

【分子式】C₁₀H₂₃B

【分子量】154.10362

【元素组成】C 77.94% H 15.04% B 7.02%

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 reaction of 4-hydroxy-1-octyne (I), with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II), which is converted into 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane (A), trimethylamine oxide, NaOH and finally I2. The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV), which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V). The Grignard reaction of (V) with vinylmagnesium bromide (B) in THF gives 4-hydroxy-4-vinyl-1-iodo-trans-1-octene (VI), which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII). The reaction of (VII) with tert-butyllithium in ether and then with copper (1)-1-pentyne-tributylphosphine (C) in HMPT affords the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether - THF giving trimethylsilyl-9-oxo-11alpha,16-bistrimethylsilyloxy-16-vinyl-5-cis-13-trans-prostadienoate (X). The hydrolysis of (X) with acetic acid in THF-water yields 9-oxo-11alpha,16-dihydroxy-16-vinyl-5-cis-13-trans-prostadienoic acid (XI), which is finally methylated with diazomethane in ether.

参考文献中间体

合成目标

【1】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Novel prostaglandin compounds. ES 475787; FR 2410648; GB 2009173; US 4198521 .
【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
(B)	16524	bromo(vinyl)magnesium	1826-67-1	C₂H₃BrMg	详情	详情
(A)	20452	bis(1,2-dimethylpropyl)borane	132509-17-2	C₁₀H₂₃B	详情	详情
(I)	29312	1-octyn-4-ol		C₈H₁₄O	详情	详情
(II)	36018	[(1-butyl-3-butynyl)oxy](trimethyl)silane; 1-butyl-3-butynyl trimethylsilyl ether		C₁₁H₂₂OSi	详情	详情
(III)	36019	(E)-1-butyl-4-iodo-3-butenyl trimethylsilyl ether; [[(E)-1-butyl-4-iodo-3-butenyl]oxy](trimethyl)silane		C₁₁H₂₃IOSi	详情	详情
(IV)	29315	(E)-1-iodo-1-octen-4-ol		C₈H₁₅IO	详情	详情
(V)	29316	(E)-1-iodo-1-octen-4-one		C₈H₁₃IO	详情	详情
(VI)	29317	(5E)-3-butyl-6-iodo-1,5-hexadien-3-ol		C₁₀H₁₇IO	详情	详情
(VII)	36020	(E)-1-butyl-4-iodo-1-vinyl-3-butenyl trimethylsilyl ether; [[(E)-1-butyl-4-iodo-1-vinyl-3-butenyl]oxy](trimethyl)silane		C₁₃H₂₅IOSi	详情	详情
(VIII)	36021	[(1E)-4-butyl-4-[(trimethylsilyl)oxy]-1,5-hexadienyl](1-pentynyl)copper		C₁₈H₃₂CuOSi	详情	详情
(IX)	36022	trimethylsilyl (Z)-7-[(3R)-5-oxo-3-[(trimethylsilyl)oxy]-1-cyclopenten-1-yl]-5-heptenoate		C₁₈H₃₂O₄Si₂	详情	详情
(X)	36023	trimethylsilyl (Z)-7-[(1R,2R,3R)-2-[(1E)-4-butyl-4-[(trimethylsilyl)oxy]-1,5-hexadienyl]-5-oxo-3-[(trimethylsilyl)oxy]cyclopentyl]-5-heptenoate		C₃₁H₅₈O₅Si₃	详情	详情
(XI)	36024	(Z)-7-[(1R,2R,3R)-2-[(1E)-4-butyl-4-hydroxy-1,5-hexadienyl]-3-hydroxy-5-oxocyclopentyl]-5-heptenoic acid		C₂₂H₃₄O₅	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：(VI)

Ketoester (II) was prepared by condensation of dimethyl carbonate with 5-methoxy-2-tetralone (I) in the presence of NaOMe. The alkylation of (II) with allyl bromide using two equivalents of LDA at -78 C proceeded selectively on the C-3 position to give (III). Further decarbomethoxylation of (III) was carried out with LiCl in moist DMSO at high temperature, and the resulting ketone (IV) was converted to ethylene ketal (V) with ethylene glycol and p-TsOH. Then, hydroboration of (V) with disiamyl borane (VI) in cold THF, followed by oxidation of borane (VII) with H2O2-NaOH furnished the primary alcohol (VIII). After Jones oxidation of alcohol (VIII), the resulting acid (IX) was esterified with MeOH and H2SO4 to give ketoester (X). Subsequent cyclization of (X) with benzylamine (XI) and AcOH in refluxing benzene afforded the intermediate tricyclic enamide (XII), which was sequentially reduced with LiAlH4 to enamine (XIII), and then with NaBH4 in the presence of AcOH to furnish a mixture of cis and trans octahydrobenzo[g]quinolines (XIV). Separation of the major trans isomer by flash chromatography was followed by hydrogenolysis of the benzyl group over Pd/C, yielding the secondary amine (XV), whitch was N-alkylated with propargyl bromide (XVI) in hot DMF to give (XVII).

参考文献中间体

合成目标

【1】 Tagmatarchis, N.; Thermos, K.; Katerinopoulos, H.E.; N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: Synthesis and adrenergic and dopaminergic activity studies. J Med Chem 1998, 41, 21, 4165.

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)	14647	5-methoxy-3,4-dihydro-2(1H)-naphthalenone	32940-15-1	C₁₁H₁₂O₂	详情	详情
(II)	20448	methyl 5-methoxy-2-oxo-1,2,3,4-tetrahydro-1-naphthalenecarboxylate		C₁₃H₁₄O₄	详情	详情
(III)	20449	methyl 3-allyl-5-methoxy-2-oxo-1,2,3,4-tetrahydro-1-naphthalenecarboxylate		C₁₆H₁₈O₄	详情	详情
(IV)	20450	3-allyl-5-methoxy-3,4-dihydro-2(1H)-naphthalenone		C₁₄H₁₆O₂	详情	详情
(V)	20451	3'-Allyl-5'-methoxy-1',2',3',4'-tetrahydrospiro[1,3-dioxolan-2,2'-naphthalene]		C₁₆H₂₀O₃	详情	详情
(VI)	20452	bis(1,2-dimethylpropyl)borane	132509-17-2	C₁₀H₂₃B	详情	详情
(VII)	20453	B-[3-[5'-Methoxy-1',2',3',4'-tetrahydrospiro[1,3-dioxolan-2,2'-naphthalen]-3'-yl]propyl]-B,B-bis(1,2-dimethylpropyl)borane		C₂₆H₄₃BO₃	详情	详情
(VIII)	20454	3-[5'-Methoxy-1',2',3',4'-tetrahydrospiro[1,3-dioxolan-2,2'-naphthalen]-3'-yl]propan-1-ol		C₁₆H₂₂O₄	详情	详情
(IX)	20455	3-(8-methoxy-3-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)propionic acid		C₁₄H₁₆O₄	详情	详情
(X)	20456	methyl 3-(8-methoxy-3-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)propanoate		C₁₅H₁₈O₄	详情	详情
(XI)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(XII)	20458	1-benzyl-6-methoxy-3,4,4a,5-tetrahydrobenzo[g]quinolin-2(1H)-one		C₂₁H₂₁NO₂	详情	详情
(XIII)	20459	1-benzyl-6-methoxy-1,2,3,4,4a,5-hexahydrobenzo[g]quinoline; 1-benzyl-1,2,3,4,4a,5-hexahydrobenzo[g]quinolin-6-yl methyl ether		C₂₁H₂₃NO	详情	详情
(XIV)	20460	1-benzyl-6-methoxy-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline; 1-benzyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl methyl ether		C₂₁H₂₅NO	详情	详情
(XV)	20461	(4aS,10aS)-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl methyl ether; (4aS,10aS)-6-methoxy-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline		C₁₄H₁₉NO	详情	详情
(XVI)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情
(XVII)	20463	(4aS,10aS)-1-(2-propynyl)-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl methyl ether; (4aS,10aS)-6-methoxy-1-(2-propynyl)-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline		C₁₇H₂₁NO	详情	详情

Extended Information