1-benzyl 3-(tert-butyl) (3S)-2-{(2R)-2-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]undecanoyl}tetrahydro-1,3(2H)-pyridazinedicarboxylate -Drug Synthesis Database

【结构式】

【分子编号】56886

【品名】1-benzyl 3-(tert-butyl) (3S)-2-{(2R)-2-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]undecanoyl}tetrahydro-1,3(2H)-pyridazinedicarboxylate

【CA登记号】

【分子式】C₃₂H₄₇Cl₃N₂O₇

【分子量】678.09256

【元素组成】C 56.68% H 6.99% Cl 15.68% N 4.13% O 16.52%

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：(X)

Acylation of the chiral oxazolidinone (I) with undecanoyl chloride furnished the N-acyl oxazolidinone (II). The lithium enolate of (II) was diastereoselectively alkylated with tert-butyl bromoacetate (III) producing (IV) as the major isomer. Then, removal of the chiral auxiliary of (IV) with lithium benzyloxide yielded benzyl ester (V). Acidic cleavage of the tert-butyl ester group of (V) provided carboxylic acid (VI), which was subsequently converted to the trichloroethyl ester (VII) via formation of the corresponding acid chloride, followed by treatment with trichloroethanol. After removal of the benzyl ester group of (VII) by hydrogenolysis, chlorination by means of oxalyl chloride gave acid chloride (VIII). This was then coupled with the protected (S)-perhydropyrazine-3-carboxylic acid (IX) to afford amide (X).

参考文献中间体

合成目标

【1】 Tamaki, K.; et al.; Synthesis and structure-activity relationships of gelatinase inhibitors derived from Matlystatins. Chem Pharm Bull 1995, 43, 11, 1883.

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)	12867	(4S)-4-Isopropyl-1,3-oxazolidin-2-one; (R)-4-Isopropyl-2-oxazolidinone	17016-83-0	C₆H₁₁NO₂	详情	详情
(II)	56879	(4S)-4-isopropyl-3-undecanoyl-1,3-oxazolidin-2-one		C₁₇H₃₁NO₃	详情	详情
(III)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(IV)	56880	tert-butyl (3R)-3-{[(4S)-4-isopropyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}dodecanoate		C₂₃H₄₁NO₅	详情	详情
(V)	56881	1-benzyl 4-(tert-butyl) (2R)-2-nonylbutanedioate		C₂₄H₃₈O₄	详情	详情
(VI)	56882	(3R)-3-[(benzyloxy)carbonyl]dodecanoic acid		C₂₀H₃₀O₄	详情	详情
(VII)	56883	1-benzyl 4-(2,2,2-trichloroethyl) (2R)-2-nonylbutanedioate		C₂₂H₃₁Cl₃O₄	详情	详情
(VIII)	56884	2,2,2-trichloroethyl (3R)-3-(chlorocarbonyl)dodecanoate		C₁₅H₂₄Cl₄O₃	详情	详情
(IX)	56885	1-benzyl 3-(tert-butyl) (3S)tetrahydro-1,3(2H)-pyridazinedicarboxylate		C₁₇H₂₄N₂O₄	详情	详情
(X)	56886	1-benzyl 3-(tert-butyl) (3S)-2-{(2R)-2-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]undecanoyl}tetrahydro-1,3(2H)-pyridazinedicarboxylate		C₃₂H₄₇Cl₃N₂O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Reductive cleavage of the trichlorethyl ester (X) using zinc powder and ammonium acetate gave acid (XI). This was then coupled to O-benzyl hydroxylamine in the presence of diethylphosphoryl cyanide (DEPC) to afford hydroxamate (XII). After deprotection of the tert-butyl ester group of (XII), the resultant acid (XIII) was converted to amide (XIV) by DEPC-mediated coupling with methylamine. The title compound was finally obtained by catalytic hydrogenolysis of the protected precursor (XIV) in the presence of Pd/C.

参考文献中间体

合成目标

【1】 Sugimura, M.; Tamaki, K.; Tanzawa, K.; Kobayashi, T. (Sankyo Co., Ltd.); Collagenase inhibitor agents. JP 1995002797 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	56886	1-benzyl 3-(tert-butyl) (3S)-2-{(2R)-2-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]undecanoyl}tetrahydro-1,3(2H)-pyridazinedicarboxylate	C₃₂H₄₇Cl₃N₂O₇	详情	详情
(XI)	56887	(3R)-3-{[(6S)-2-[(benzyloxy)carbonyl]-6-(tert-butoxycarbonyl)tetrahydro-1(2H)-pyridazinyl]carbonyl}dodecanoic acid	C₃₀H₄₆N₂O₇	详情	详情
(XII)	56888	1-benzyl 3-(tert-butyl) (3S)-2-((2R)-2-{2-[(benzyloxy)amino]-2-oxoethyl}undecanoyl)tetrahydro-1,3(2H)-pyridazinedicarboxylate	C₃₇H₅₃N₃O₇	详情	详情
(XIII)	56889	(3S)-2-((2R)-2-{2-[(benzyloxy)amino]-2-oxoethyl}undecanoyl)-1-[(benzyloxy)carbonyl]hexahydro-3-pyridazinecarboxylic acid	C₃₃H₄₅N₃O₇	详情	详情
(XIV)	56890	benzyl (3S)-2-((2R)-2-{2-[(benzyloxy)amino]-2-oxoethyl}undecanoyl)-3-[(methylamino)carbonyl]tetrahydro-1(2H)-pyridazinecarboxylate	C₃₄H₄₈N₄O₆	详情	详情

Extended Information