tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate -Drug Synthesis Database

【结构式】

【分子编号】14540

【品名】tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate

【CA登记号】

【分子式】C₁₄H₁₉NO₃

【分子量】249.3098

【元素组成】C 67.45% H 7.68% N 5.62% O 19.25%

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：(XXV)

3) The condensation of N-(tert-butoxycarbonyl)-L-phenylalaninal (XXV) with 2-(trimethylsilyl)thiazole (XXVI) by means of tetrabutylammonium fluoride gives the thiazole derivative (XXVII), which is cleaved by reaction with methyl iodide (formation of the thiazolium derivative) and treated with NaBH4 and HgCl2 to afford the protected 3(S)-amino-2(S)-hydroxy-4-phenylbutanal (XXVIII). Finally, this compound is reductocondensed with isoquinoline (XI) by means of sodium cyanoborohydride to yield the protected condensation product (XII), already obtained in scheme 16810301a.

参考文献中间体

合成目标

【1】 Parkes, K.E.B.; Bushnell, D.J.; Crackett, P.H.; et al.; Studies toward the large-scale synthesis of the HIV proteinase inhibitor Ro 31-8959. J Org Chem 1994, 59, 13, 3656.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	14527	(3S,4aS,8aS)-N-(tert-butyl)-2-((2R,3S)-3-[[(2,2-dimethylpropanoyl)oxy]amino]-2-hydroxy-4-phenylbutyl)decahydro-3-isoquinolinecarboxamide		C₂₉H₄₇N₃O₄	详情	详情
(XXV)	14540	tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate		C₁₄H₁₉NO₃	详情	详情
(XXVI)	10720	2-(Trimethylsilyl)-1,3-thiazole	79265-30-8	C₆H₁₁NSSi	详情	详情
(XXVII)	14542	tert-butyl (1S,2S)-1-benzyl-2-hydroxy-2-(1,3-thiazol-2-yl)ethylcarbamate		C₁₇H₂₂N₂O₃S	详情	详情
(XXVIII)	14543	tert-butyl N-[(1S,2S)-1-benzyl-2-hydroxy-3-oxopropyl]carbamate		C₁₅H₂₁NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

2) Intermediate (IX) can also be obtained as follows: The cyclization of 4-cyanobenzoic acid methyl ester (XII) with acetylene at 15 Atm by means of cobaltocene in toluene at 180 C gives 4-(2-pyridyl)benzoic acid methyl ester (XIII), which is saponified with NaOH in methanol to the corresponding acid (XIV). The activation of (XIV) with isobutyl chloroformate yields the mixed anhydride (XV), which is condensed with N-(tert-butoxycarbonyl)-L-phenylalaninal (XVI) and KCN in dichloromethane, affording (XVII). The reaction of (XVII) with tert-butyl carbazate (V) by means of acetic acid in methanol gives hydrazone (XVIII), which is reduced to hydrazine (XIX) by means of sodium cyanoborohydride in THF. The isomerization of (XIX) by means of 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTDE) in hot diglyme yields hydrazide (XX), which is finally reduced to intermediate (IX) with diisobutylaluminum hydride in dichloromethane/THF.

参考文献中间体

合成目标

【1】 Fassler, A.; Steiner, H.; Bold, G.; Capraro, H.-G. (Novartis AG); Process for the preparation of hydrazine derivs. useful as intermediates for the preparation of peptide analogues. WO 9746514 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23634	acetylene	74-86-2	C₂H₂	详情	详情
(V)	10893	tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate	870-46-2	C₅H₁₂N₂O₂	详情	详情
(IX)	23445	tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzyl]-1-hydrazinecarboxylate		C₃₂H₄₂N₄O₅	详情	详情
(XII)	10169	methyl 4-cyanobenzoate；4-Cyanobenzoic acid methyl ester	1129-35-7	C₉H₇NO₂	详情	详情
(XIII)	23449	methyl 4-(2-pyridinyl)benzoate		C₁₃H₁₁NO₂	详情	详情
(XIV)	23450	4-(2-pyridinyl)benzoic acid		C₁₂H₉NO₂	详情	详情
(XV)	23451	4-(2-Pyridyl)benzoic acid isobutoxycarbonyl anhydride		C₁₇H₁₇NO₄	详情	详情
(XVI)	14540	tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate		C₁₄H₁₉NO₃	详情	详情
(XVII)	23453	(1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-cyano-3-phenylpropyl 4-(2-pyridinyl)benzoate		C₂₇H₂₇N₃O₄	详情	详情
(XVIII)	23454	tert-butyl 2-((E,2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butylidene)-1-hydrazinecarboxylate		C₃₂H₃₈N₄O₆	详情	详情
(XIX)	23455	tert-butyl 2-((2S,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butyl)-1-hydrazinecarboxylate		C₃₂H₄₀N₄O₆	详情	详情
(XX)	23457	tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzoyl]-1-hydrazinecarboxylate		C₃₂H₄₀N₄O₆	详情	详情

Extended Information