(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide -Drug Synthesis Database

【结构式】

【分子编号】57913

【品名】(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide

【CA登记号】

【分子式】C₁₇H₂₇FN₂O₄S

【分子量】374.4768632

【元素组成】C 54.53% H 7.27% F 5.07% N 7.48% O 17.09% S 8.56%

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：(VII)

The condensation of L-valine (I) with 4-fluorobenzenesulfonyl chloride (II) by means of NaOH in THF/water gives N-(4-fluorobenzenesulfonyl)-L-valine (III), which is esterified with N-hydroxysuccinimide (IV) by means of EDC in dichloromethane to yield the activated ester (V). The condensation of (V) with L-leucinol (VI) by means of TEA in dichloromethane affords the N-(4-fluorobenzenesulfonyl)-L-valyl-L-leucinol (VII), which is finally oxidized with the SO3/Pyridine complex in DMSO/dichloromethane to provide the target leucinal derivative.

参考文献中间体

合成目标

【1】 Fukiage, C.; et al.; SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses. Biochim Biophys Acta 1997, 1361, 3, 304.
【2】 Fukiage, C.; Azuma, M.; Inoue, J.; Nakamura, M.; Yoshida, Y. (Senju Pharmaceuticals Co., Ltd.); Angiogenesis inhibitor. EP 0771565; EP 0927716; EP 0928786; JP 1998147564; JP 1998147566; JP 2001233847; US 6057290; US 6214800 .

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)	37828	L-2-Amino-3-methylbutyric acid; L-2-Aminoisovaleric acid; 2-Aminoisovaleric acid; L-2-Amino-3-methylbutyric acid; L-alpha-Aminoisovaleric acid; L-valine; (S)-(+)-Valine; (S)-alpha-Aminoisovaleric acid	72-18-4	C₅H₁₁NO₂	详情	详情
(II)	12292	4-Fluorobenzenesulfonyl chloride	349-88-2	C₆H₄ClFO₂S	详情	详情
(III)	57911	(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-3-methylbutanoic acid		C₁₁H₁₄FNO₄S	详情	详情
(IV)	10264	1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione	6066-82-6	C₄H₅NO₃	详情	详情
(V)	57912	N-((1S)-1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-2-methylpropyl)-4-fluorobenzenesulfonamide		C₁₅H₁₇FN₂O₆S	详情	详情
(VI)	18171	L-(+)-leucinol; (S)-2-amino-4-methyl-1-pentanol; (2S)-2-amino-4-methyl-1-pentanol	7533-40-6	C₆H₁₅NO	详情	详情
(VII)	57913	(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide		C₁₇H₂₇FN₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Swern oxidation of the sulfonyl dipeptide alcohol (I) in the presence of sulfur trioxide-pyridine complex and DMSO affords aldehyde (II). This is then condensed with (dimethylamino)acetohydrazide (III) to produce the target N-acyl hydrazone

参考文献中间体

合成目标

【1】 Nakamura, M.; Inoue, J.; Exploration of peptidyl hydrazones as water-soluble calpain inhibitors. Bioorg Med Chem Lett 2002, 12, 12, 1603.

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)	57913	(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide		C₁₇H₂₇FN₂O₄S	详情	详情
(II)	60378	(2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-formyl-3-methylbutyl]-3-methylbutanamide		C₁₇H₂₅FN₂O₄S	详情	详情
(III)	40924	2-(dimethylamino)acetohydrazide	539-64-0	C₄H₁₁N₃O	详情	详情

Extended Information