tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】44938

【品名】tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate

【CA登记号】

【分子式】C₂₅H₃₅N₃O₇S

【分子量】521.63492

【元素组成】C 57.56% H 6.76% N 8.06% O 21.47% S 6.15%

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：(V)

Reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III), which is condensed with 4-nitrophenylsulfonyl chloride (IV) and TEA in hot toluene to yield the sulfonamide (V). Deprotection of (V) with HCl hot toluene/water affords the primary amine (VI), which is condensed with imidazole-1-carboxylic acid 3(S)-tetrahydrofuryl ester (VII) [prepared by reaction of tetrahydrofuran-3(S)-ol (VIII) with carbonyldiimidazole (CDI) in ethyl acetate] to provide the corresponding carbamate (IX). Finally, the nitro group of (IX) is reduced with H2 over Pd/C in ethyl acetate to afford the target compound.

参考文献中间体

合成目标

【1】 Deininger, D.D.; O'Callaghan, J.; McGuie, S.; Singh, H.; Robertson, M.S.; Rodgers, K.; Tung, R.D.; Al-Farhan, E.; Rout, S.J. (Glaxo Group Ltd.); Process for the synthesis of HIV protease inhibitors. WO 9948885 .

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)	19730	tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate	98737-29-2	C₁₅H₂₁NO₃	详情	详情
(II)	13306	2-Methyl-1-propanamine; Isobutylamine	78-81-9	C₄H₁₁N	详情	详情
(III)	44417	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate	160232-08-6	C₁₉H₃₂N₂O₃	详情	详情
(IV)	15809	4-nitrobenzenesulfonyl chloride	98-74-8	C₆H₄ClNO₄S	详情	详情
(V)	44938	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate		C₂₅H₃₅N₃O₇S	详情	详情
(VI)	44939	N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-nitrobenzenesulfonamide	590-90-9	C₂₀H₂₇N₃O₅S	详情	详情
(VII)	44940	(3S)tetrahydro-3-furanyl 1H-imidazole-1-carboxylate		C₈H₁₀N₂O₃	详情	详情
(VIII)	44420	(3S)-tetrahydro-3-furanol; (S)-3-Hydroxytetrahydrofuran	86087-23-2	C₄H₈O₂	详情	详情
(IX)	44423	(3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate		C₂₅H₃₃N₃O₈S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

The reaction of the chiral epoxide (I) with isobutylamine (II) in refluxing ethanol gives the secondary amine (III), which is condensed with 4-nitrophenylsulfonyl chloride (XII) and TEA in hot toluene, yielding sulfonamide (XIV). Deprotection of (XIV) with HCl in hot toluene/water affords the primary amine (XV), which is condensed with imidazole-1-carboxylic acid 3(S)-tetrahydrofuryl ester (XVI) -- prepared by reaction of tetrahydrofuran-3(S)-ol (VIII) with carbonyldiimidazole (CDI) in ethyl acetate -- to provide intermediate (XIII).

参考文献中间体

合成目标

【1】 Martin, L.; Castaner, R.M.; Sorbera, L.A.; Castaner, J.; Fosamprenavir. Drugs Fut 2001, 26, 3, 224.
【2】 Deininger, D.D.; O'Callaghan, J.; McGuie, S.; Singh, H.; Robertson, M.S.; Rodgers, K.; Tung, R.D.; Al-Farhan, E.; Rout, S.J. (Glaxo Group Ltd.); Process for the synthesis of HIV protease inhibitors. WO 9948885 .

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)	19730	tert-butyl (1S)-1-[(2S)oxiranyl]-2-phenylethylcarbamate	98737-29-2	C₁₅H₂₁NO₃	详情	详情
(II)	13306	2-Methyl-1-propanamine; Isobutylamine	78-81-9	C₄H₁₁N	详情	详情
(III)	44417	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate	160232-08-6	C₁₉H₃₂N₂O₃	详情	详情
(VIII)	44420	(3S)-tetrahydro-3-furanol; (S)-3-Hydroxytetrahydrofuran	86087-23-2	C₄H₈O₂	详情	详情
(XII)	15809	4-nitrobenzenesulfonyl chloride	98-74-8	C₆H₄ClNO₄S	详情	详情
(XIII)	44423	(3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate		C₂₅H₃₃N₃O₈S	详情	详情
(XIV)	44938	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate		C₂₅H₃₅N₃O₇S	详情	详情
(XV)	44939	N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-nitrobenzenesulfonamide	590-90-9	C₂₀H₂₇N₃O₅S	详情	详情
(XVI)	10264	1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione	6066-82-6	C₄H₅NO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：（V）

参考文献中间体

合成目标

【1】 Goyvaerts NMF, Wigerinck PTBP, et al.2005. Process for the preparation of (3R,3aS,6aR)-hexahydrofuro [2,3-b] funur-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl](isobutyl) amino}l-benzyl-2-hydroxy-propylcarbamate from l-oxirayl-2-phenylethylcarbamates. W0 2005063770
【2】 Surleraux DLNG, Tahri A.et aL 2005. Discovery and selection ofTMC114,a next genention HIV-1 protease inhibitor.JMed Chem, 48. 1813~1822

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（V）	44938	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate		C₂₅H₃₅N₃O₇S	详情	详情
(I)	32815	(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-ol		C₆H₁₀O₃	详情	详情
(II)	32812	1-([[(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy)-2,5-pyrrolidinedione		C₁₁H₁₃NO₇	详情	详情
(III)	66218	Carbamic acid,[(1R)-1-(2R)-oxiranyl-2-phenylethyl]-, 1,1-dimethylethyl ester, rel- ;Carbamicacid, (1-oxiranyl-2-phenylethyl)-, 1,1-dimethylethyl ester, (R,R)-(à)-;Carbamic acid,(1-oxiranyl-2-phenylethyl)-, 1,1-dimethylethyl ester, (R,R)-	98818-34-9	C₁₅H₂₁NO₃	详情	详情
(IV)	44417	tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate	160232-08-6	C₁₉H₃₂N₂O₃	详情	详情
(VI)	45533	4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutylbenzenesulfonamide		C₂₀H₂₉N₃O₃S	详情	详情

Extended Information