N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-nitrobenzenesulfonamide -Drug Synthesis Database

【结构式】

【分子编号】44939

【品名】N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-nitrobenzenesulfonamide

【CA登记号】590-90-9

【分子式】C₂₀H₂₇N₃O₅S

【分子量】421.5176

【元素组成】C 56.99% H 6.46% N 9.97% O 18.98% S 7.61%

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：(VI)

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：(XV)

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

Extended Information