tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】45698

【品名】tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate

【CA登记号】1638-63-7

【分子式】C₃₀H₄₈N₄O₆S

【分子量】592.80048

【元素组成】C 60.78% H 8.16% N 9.45% O 16.19% S 5.41%

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：(IX)

Coupling of carboxylic acid (I) with tert-butylamine (II) by means of EDC-HOBt in CH2Cl2 affords carboxamide (III), whose Boc group is removed by treatment with HCl/dioxane to provide compound (IV). Coupling of thiazolidine (IV) to Boc-protected allophenylnorstatine (V) by means of DCC and HOBt in EtOAc provides derivative (VI), whose is deprotected by treatment with HCl/dioxane to yield (VII), which is then coupled to Boc-Val-OH (VIII) with EDC-HOBt in DMF to furnish compound (IX). On the other hand, aminophenol derivative (XI) is condensed with benzyl chloroacetate (XII) in DMF in the presence of K2CO3 to furnish derivative (XIII), which is then debenzylated by hydrogenation over Pd/C in MeOH to yield acetic acid derivative (XIV). Finally, the Boc group of (IX) is removed with HCl/dioxane and the resulting amine (X) is coupled to carboxylic acid (XIV) by first treatment with N-hydroxy-5-norbornene-2,3-dicarboximide (HONB) and DCC in CH2Cl2 followed by treatment with Et3N in DMF. Alternatively, the coupling can be performed by means of EDC and HOBt in DMF.

参考文献中间体

合成目标

【1】 Takaku, H.; Hattori, N.; Mimoto, T.; et al.; Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere. Chem Pharm Bull 2000, 48, 9, 1310.
【2】 Terashima, K.; Mimoto, T.; Takaku, H.; Nojima, S.; Kiso, Y. (Japan Energy Corp.); Novel tripeptide cpds. and anti-AIDS drugs. EP 0900566; WO 9829118 .

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)	34777	(4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid		C₁₁H₁₉NO₄S	详情	详情
(II)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(III)	45695	tert-butyl (4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidine-3-carboxylate		C₁₅H₂₈N₂O₃S	详情	详情
(IV)	15836	N-t-BOC-(2R,3R)-3-Amino-2-hydroxy-4-phenylbutyric acid; (2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyric acid	116661-86-0	C₁₅H₂₁NO₅	详情	详情
(V)	45697	tert-butyl (1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropylcarbamate		C₂₅H₃₉N₃O₅S	详情	详情
(VI)	45698	tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate	1638-63-7	C₃₀H₄₈N₄O₆S	详情	详情
(VII)	29294	(4R)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide		C₂₀H₃₁N₃O₃S	详情	详情
(VIII)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(IX)	45698	tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate	1638-63-7	C₃₀H₄₈N₄O₆S	详情	详情
(X)	45699	(4R)-3-((2S,3S)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutanoyl)-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide		C₂₅H₄₀N₄O₄S	详情	详情
(XI)	45700	N,N-Dimethyl-3-aminophenol; 3-Dimethylaminophenol; m-Dimethylaminophenol	99-07-0	C₈H₁₁NO	详情	详情
(XII)	45701	benzyl 2-chloroacetate	140-18-1	C₉H₉ClO₂	详情	详情
(XIII)	45702	benzyl 2-[3-(dimethylamino)phenoxy]acetate		C₁₇H₁₉NO₃	详情	详情
(XIV)	45703	2-[3-(dimethylamino)phenoxy]acetic acid		C₁₀H₁₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

参考文献中间体

合成目标

【1】 Takaku, H.; Hattori, N.; Mimoto, T.; et al.; Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere. Chem Pharm Bull 2000, 48, 9, 1310.
【2】 Terashima, K.; Mimoto, T.; Takaku, H.; Nojima, S.; Kiso, Y. (Japan Energy Corp.); Novel tripeptide cpds. and anti-AIDS drugs. EP 0900566; WO 9829118 .

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)	34777	(4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid		C₁₁H₁₉NO₄S	详情	详情
(II)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(III)	45695	tert-butyl (4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidine-3-carboxylate		C₁₅H₂₈N₂O₃S	详情	详情
(IV)	15836	N-t-BOC-(2R,3R)-3-Amino-2-hydroxy-4-phenylbutyric acid; (2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyric acid	116661-86-0	C₁₅H₂₁NO₅	详情	详情
(V)	45697	tert-butyl (1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropylcarbamate		C₂₅H₃₉N₃O₅S	详情	详情
(VI)	45698	tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate	1638-63-7	C₃₀H₄₈N₄O₆S	详情	详情
(VII)	29294	(4R)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide		C₂₀H₃₁N₃O₃S	详情	详情
(VIII)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(IX)	45698	tert-butyl (1S)-1-[[((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-5,5-dimethyl-1,3-thiazolidin-3-yl]-2-hydroxy-3-oxopropyl)amino]carbonyl]-2-methylpropylcarbamate	1638-63-7	C₃₀H₄₈N₄O₆S	详情	详情
(X)	45699	(4R)-3-((2S,3S)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-hydroxy-4-phenylbutanoyl)-N-(tert-butyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide		C₂₅H₄₀N₄O₄S	详情	详情
(XI)	45700	N,N-Dimethyl-3-aminophenol; 3-Dimethylaminophenol; m-Dimethylaminophenol	99-07-0	C₈H₁₁NO	详情	详情
(XII)	45701	benzyl 2-chloroacetate	140-18-1	C₉H₉ClO₂	详情	详情
(XIII)	45702	benzyl 2-[3-(dimethylamino)phenoxy]acetate		C₁₇H₁₉NO₃	详情	详情
(XIV)	45703	2-[3-(dimethylamino)phenoxy]acetic acid		C₁₀H₁₃NO₃	详情	详情

Extended Information