(2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid -Drug Synthesis Database

【结构式】

【分子编号】48375

【品名】(2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid

【CA登记号】

【分子式】C₁₀H₁₉NO₄

【分子量】217.2652

【元素组成】C 55.28% H 8.81% N 6.45% O 29.46%

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：(XIV)

The thiazole amino acid (XIX) was prepared by a similar method as above, consisting of conversion of N-Boc-D-valine (XIV) to the corresponding amide (XV) followed by thionation to (XVI). Condensation of thioamide (XVI) with ethyl bromopyruvate (X) and subsequent acid dehydration gave thiazole (XVIII). Basic hydrolysis of the ethyl ester group of (XVIII) then gave acid (XIX). Coupling of the N-Boc-amino acid (XIX) with aminoester (XIII) produced the corresponding amide (XX). Further acid cleavage of the Boc protecting group gave (XXI).

参考文献中间体

合成目标

【1】 Xia, Z.; Smith, C.D.; Total synthesis of dendroamide A, a novel cyclic peptide that reverses multiple drug resistance. J Org Chem 2001, 66, 10, 3459.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	25183	ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate	70-23-5	C₅H₇BrO₃	详情	详情
(XIII)	48367	ethyl 2-[(1R)-1-aminoethyl]-1,3-thiazole-4-carboxylate		C₈H₁₂N₂O₂S	详情	详情
(XIV)	48375	(2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(XV)	48368	tert-butyl (1R)-1-(aminocarbonyl)-2-methylpropylcarbamate		C₁₀H₂₀N₂O₃	详情	详情
(XVI)	48369	tert-butyl (1R)-1-(aminocarbothioyl)-2-methylpropylcarbamate		C₁₀H₂₀N₂O₂S	详情	详情
(XVII)	48370	ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-4-hydroxy-4,5-dihydro-1,3-thiazole-4-carboxylate		C₁₅H₂₆N₂O₅S	详情	详情
(XVIII)	48371	ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazole-4-carboxylate		C₁₅H₂₄N₂O₄S	详情	详情
(XIX)	48372	2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazole-4-carboxylic acid		C₁₃H₂₀N₂O₄S	详情	详情
(XX)	48373	ethyl 2-((1R)-1-[[(2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazol-4-yl)carbonyl]amino]ethyl)-1,3-thiazole-4-carboxylate		C₂₁H₃₀N₄O₅S₂	详情	详情
(XXI)	48374	ethyl 2-[(1R)-1-[([2-[(1R)-1-amino-2-methylpropyl]-1,3-thiazol-4-yl]carbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate		C₁₆H₂₂N₄O₃S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Condensation of 3,4-dichlorobenzyl bromide (I) with triphenylphosphine affords the phosphonium salt (II). The ylide obtained from (II) and butyllithium is then subjected to a Wittig reaction with N-Boc-4-piperidinone (III) to provide the benzylidene piperidine (IV). Catalytic hydrogenation of (IV) over PtO2 gives rise to the corresponding benzylpiperidine (V). After acidic Boc group cleavage in (V), the deprotected piperidine (VI) is coupled with N-Boc-D-valine (VII) in the presence of EDC to furnish amide (VIII). Further N-Boc group cleavage in (VIII) employing trifluoroacetic acid yields amino amide (IX), which is then reduced to diamine (X) by means of borane in THF. Coupling of amine (X) with 3,4,5-trimethoxyphenyl isocyanate (XI) leads to urea (XII). Finally, quaternization of the piperidine N of (XII) with iodomethane provides the title piperidinium salt.

参考文献中间体

合成目标

【1】 Kertesz, D.J.; Smith, D.B.; Hirschfeld, D.R. (F. Hoffmann-La Roche AG); Piperidine CCR-3 receptor antagonists. DE 19955793; EP 1131290; GB 2343894; JP 2002530375; US 6342509; WO 0031033 .
【2】 Wilhelm, R.S.; Smith, D.B.; Talamas, F.X.; Gong, L.; tesz, D.J. (Syntex (USA) LLC); Cyclic amine derivs.-CCR-3 receptor antagonists. US 6339087 .

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)	42911	4-(bromomethyl)-1,2-dichlorobenzene	18880-04-1	C₇H₅BrCl₂	详情	详情
(II)	58924	(3,4-dichlorobenzyl)(triphenyl)phosphonium bromide		C₂₅H₂₀BrCl₂P	详情	详情
(III)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(IV)	58925	tert-butyl 4-(3,4-dichlorobenzylidene)-1-piperidinecarboxylate		C₁₇H₂₁Cl₂NO₂	详情	详情
(V)	58926	tert-butyl 4-(3,4-dichlorobenzyl)-1-piperidinecarboxylate		C₁₇H₂₃Cl₂NO₂	详情	详情
(VI)	58927	4-(3,4-dichlorobenzyl)piperidine		C₁₂H₁₅Cl₂N	详情	详情
(VII)	48375	(2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid		C₁₀H₁₉NO₄	详情	详情
(VIII)	58928	tert-butyl (1R)-1-{[4-(3,4-dichlorobenzyl)-1-piperidinyl]carbonyl}-2-methylpropylcarbamate		C₂₂H₃₂Cl₂N₂O₃	详情	详情
(IX)	58929	(2R)-2-amino-1-[4-(3,4-dichlorobenzyl)-1-piperidinyl]-3-methyl-1-butanone		C₁₇H₂₄Cl₂N₂O	详情	详情
(X)	58930	(2R)-1-[4-(3,4-dichlorobenzyl)-1-piperidinyl]-3-methyl-2-butanamine; (1R)-1-{[4-(3,4-dichlorobenzyl)-1-piperidinyl]methyl}-2-methylpropylamine		C₁₇H₂₆Cl₂N₂	详情	详情
(XI)	58931	3,4,5-trimethoxyphenyl isocyanate; 5-isocyanato-1,2,3-trimethoxybenzene		C₁₀H₁₁NO₄	详情	详情
(XII)	58933	7-Octene-1,2-diol		C₈H₁₆O₂	详情	详情

Extended Information