(2S)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-isopropyl-N-methyl-4-pentenamide -Drug Synthesis Database

【结构式】

【分子编号】50586

【品名】(2S)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-isopropyl-N-methyl-4-pentenamide

【CA登记号】

【分子式】C₁₈H₂₇NO₂

【分子量】289.41792

【元素组成】C 74.7% H 9.4% N 4.84% O 11.06%

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：(XLIV)

The chiral azido intermediate (XXXIV) can also be obtained as follows: Reaction of (+)-pseudoephedrine isovaleramide (XLIII) with allyl bromide (XXI) by means of LDA in THF gives the pentenoyl amide (XLIV), which is treated with NBS in DME/water to yield the spiro compound (XLV). Hydrolysis of the bromomethyl group of (XLV) with tetrabutylammonium acetate and K2CO3 affords the carbinol (XLVI), which is oxidized to aldehyde (XLVII) with SO3/pyridine and TEA in DMSO/dichloromethane. Condensation of (XLVII) with the propyl chloride intermediate (XXX) by means of Mg, dibromoethane and CeCl3 in refluxing THF provides the already reported chiral hydroxylactone (XXXII), which is treated first with 4-bromobenzenesulfonyl chloride and then with NaN3 to give the desired azido derivative (XXXIV).

参考文献中间体

合成目标

【1】 Mealy, N.E.; Castañer, R.M.; Silvestre, J.S.; Castañer, J.; Aliskiren Fumarate. Drugs Fut 2001, 26, 12, 1139.
【2】 Carey, J.S.; Sandham, D.A.; Taylor, R.J.; Fassler, A.; A convergent synthesis of the renin inhibitor CGP60536B. Tetrahedron Lett 2000, 41, 51, 10091.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXI)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XXX)	50574	4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)benzene; 3-[5-[(2R)-2-(chloromethyl)-3-methylbutyl]-2-methoxyphenoxy]propyl methyl ether	324763-39-5	C₁₇H₂₇ClO₃	详情	详情
(XXXII)	50576	(3S,5S)-5-[(1R,3S)-1-hydroxy-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone		C₂₅H₄₀O₆	详情	详情
(XXXIV)	50578	(3S,5S)-5-[(1S,3S)-1-azido-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone		C₂₅H₃₉N₃O₅	详情	详情
(XLIII)	50585	N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N,3-dimethylbutanamide		C₁₅H₂₃NO₂	详情	详情
(XLIV)	50586	(2S)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-isopropyl-N-methyl-4-pentenamide		C₁₈H₂₇NO₂	详情	详情
(XLV)	50587	(2S,3S,5R,7S,9S)-7-(bromomethyl)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane		C₁₈H₂₆BrNO₂	详情	详情
(XLVI)	50588	[(2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]non-7-yl]methanol		C₁₈H₂₇NO₃	详情	详情
(XLVII)	50589	(2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane-7-carbaldehyde		C₁₈H₂₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

参考文献中间体

合成目标

【1】 Sandham DA, Taylor RJ, Carey JS, et al. 2000. A convergent synthesis of the renin inhibitory CGP60536B. Tetrahedron Lett, 41(51): 10091～10094

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	50585	N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N,3-dimethylbutanamide		C₁₅H₂₃NO₂	详情	详情
(I)	50580	(E)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoic acid		C₁₄H₁₈O₅	详情	详情
(II)	50583	N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-N-methylpropanamide		C₂₄H₃₃NO₅	详情	详情
(III)	50584	(2R)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-N,3-dimethylbutanamide		C₂₇H₃₉NO₅	详情	详情
(IV)	50573	(2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methyl-1-butanol		C₁₇H₂₈O₄	详情	详情
(V)	50574	4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)benzene; 3-[5-[(2R)-2-(chloromethyl)-3-methylbutyl]-2-methoxyphenoxy]propyl methyl ether	324763-39-5	C₁₇H₂₇ClO₃	详情	详情
(VII)	50586	(2S)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-isopropyl-N-methyl-4-pentenamide		C₁₈H₂₇NO₂	详情	详情
(VIII)	50587	(2S,3S,5R,7S,9S)-7-(bromomethyl)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane		C₁₈H₂₆BrNO₂	详情	详情
(IX)	50588	[(2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]non-7-yl]methanol		C₁₈H₂₇NO₃	详情	详情
(X)	50589	(2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane-7-carbaldehyde		C₁₈H₂₅NO₃	详情	详情
(XI)	50576	(3S,5S)-5-[(1R,3S)-1-hydroxy-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone		C₂₅H₄₀O₆	详情	详情
(XII)	50578	(3S,5S)-5-[(1S,3S)-1-azido-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone		C₂₅H₃₉N₃O₅	详情	详情
(XIII)	28129	3-amino-2,2-dimethylpropanamide	324763-51-1	C₅H₁₂N₂O	详情	详情
(XIV)	61613	(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide		C₃₀H₅₁N₅O₆	详情	详情

Extended Information