diallylamine;Di-2-propenylamine;N-2-Propenyl-2-propen-1-amine -Drug Synthesis Database

【结构式】

【分子编号】68044

【品名】diallylamine;Di-2-propenylamine;N-2-Propenyl-2-propen-1-amine

【CA登记号】124-02-7

【分子式】C₆H₁₁N

【分子量】97.16008

【元素组成】C 74.17% H 11.41% N 14.42%

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：(II)

Sonolisib is prepared by condensation of wortmannin (I) with diallylamine (II) in dichloromethane at room temperature .

参考文献中间体

合成目标

【1】 Powis, G. (University of Arizona). Wortmannin analogs and methods of using same. CA 2458318, EP 1435941, EP 1686124, EP 1914230, JP 2005507880, WO 2003024183.

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)	68043	1-(methoxymethyl)-6b,9a,11b-trimethyl-11-(2-oxopropyl)-7,8,10,11-tetrahydro-1H-furo[4,3,2-de]indeno[4,5-h]isochromene-3,6,9(6bH,9aH,11bH)-trione		C₂₅H₂₈O₇	详情	详情
(II)	68044	diallylamine;Di-2-propenylamine;N-2-Propenyl-2-propen-1-amine	124-02-7	C₆H₁₁N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIX)

Intermediate (XXXVIII) can be prepared by several alternative methods. Protection of diallylamine (XXXIX) with benzyl chloroformate and Et3N in CH2Cl2 yields the benzyloxycarbonyl derivative (XL), which undergoes ring-closing metathesis in the presence of Grubbs’ catalyst to give 1-Cbz-3-pyrroline (XLI). Reaction of compound (XLI) with NBS in aqueous DMSO followed by treatment of the resulting bromohydrin with 1 N NaOH leads to epoxide (XLII), which undergoes ring opening with NaN3 in aqueous dioxane to afford the racemic trans-azidoalcohol (XLIII). Resolution of rac-(XLIII) is then effected by incubation with lipase PS in the presence of vinyl acetate in i-Pr2O to give the (R,R)-acetate (XLIV) along with unreacted (S,S)-alcohol (XLIII). Methylation of (S,S)-alcohol (XLIII) with iodomethane and NaH affords ether (XLV), which is submitted to azide group reduction by means of PPh3 in THF/H2O to give amine (XLVI). Protection of amine (XLVI) with Boc2O and Et3N followed by selective removal of the Cbz group in the resulting bis-carbamate (XLVII) using poly(methylhydrosiloxane) and Pd/C in EtOH leads to the pyrrolidine (XLVIII), which is finally treated with Boc2O and Et3N .

参考文献中间体

合成目标

【1】 Kamal, A., Shaik, A.A., Sandbhor, M., Malik, M.S., Kaga, H. Chemoenzymatic synthesis of (3S,4S)- and (3R,4R)-3-methoxy-4-methylaminopyrrolidine. Tetrahedron Lett 2004, 45(43): 8057-9.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXVIII)	69233	(3S,4S)-tert-butyl 3-((tert-butoxycarbonyl)amino)-4-methoxypyrrolidine-1-carboxylate		C₁₅H₂₈N₂O₅	详情	详情
(XXXIX)	68044	diallylamine;Di-2-propenylamine;N-2-Propenyl-2-propen-1-amine	124-02-7	C₆H₁₁N	详情	详情
(XL)	69234	benzyl diallylcarbamate		C₁₄H₁₇NO₂	详情	详情
(XLI)	15923	1-Benzyloxycarbonyl-3-pyrroline;3-Pyrroline-1-carboxylicacid, benzyl ester ;N-(Benzyloxycarbonyl)-3-pyrroline;Benzyl 3-pyrroline-1-carboxylate;2H,5H-Pyrrole-1-carboxylicacid benzyl ester;2,5-Dihydropyrrole-1-carboxylic acid benzyl ester;benzyl 2,5-dihydro-1H-pyrrole-1-carboxylate	31970-04-4	C₁₂H₁₃NO₂	详情	详情
(XLII)	69235	benzyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate		C₁₂H₁₃NO₃	详情	详情
(XLIII)	69236	(3S,4S)-benzyl 3-azido-4-hydroxypyrrolidine-1-carboxylate-benzyl 3-azido-4-hydroxypyrrolidine-1-carboxylate		C₁₂H₁₄N₄O₃	详情	详情
(XLIV)	69237	(3R,4R)-benzyl 3-acetoxy-4-azidopyrrolidine-1-carboxylate		C₁₄H₁₆N₄O₄	详情	详情
(XLV)	69238	(3S,4S)-benzyl 3-azido-4-methoxypyrrolidine-1-carboxylate		C₁₃H₁₆N₄O₃	详情	详情
(XLVI)	69241	(3S,4S)-benzyl 3-amino-4-methoxypyrrolidine-1-carboxylate		C₁₃H₁₈N₂O₃	详情	详情
(XLVII)	69239	(3S,4S)-benzyl 3-((tert-butoxycarbonyl)amino)-4-methoxypyrrolidine-1-carboxylate		C₁₈H₂₆N₂O₅	详情	详情
(XLVIII)	69240	tert-butyl ((3S,4S)-4-methoxypyrrolidin-3-yl)carbamate		C₁₀H₂₀N₂O₃	详情	详情

Extended Information