tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate -Drug Synthesis Database

【结构式】

【分子编号】37352

【品名】tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate

【CA登记号】

【分子式】C₁₂H₂₃NO₃

【分子量】229.31956

【元素组成】C 62.85% H 10.11% N 6.11% O 20.93%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(V)

Selective O-alkylation of trans-4-aminocyclohexanol (I) was effected by protection of the amino group as the triazinone (III) upon treatment with N,N-dimethylurea and formaldehyde. Subsequent alkylation of (III) with tert-butyl bromoacetate under phase-transfer conditions afforded ether (IV). The protecting group of (IV) was then removed by treatment with ammonium chloride.

参考文献中间体

合成目标

【1】 Ono, S.; Yoshida, T.; Ashimori, A.; Kosaka, K.; Okada, T.; Maeda, K.; Eda, M.; Mori, F.; Inoue, Y.; Ebisu, H.; Imada, T.; Ikegawa, R.; Wang, F.; Nakamura, N. (Welfide Corporation); Novel fused-ring carboxylic acid cpds. or salt thereof,and medicinal use thereof. EP 0712844; JP 1996053398; JP 1996231548; US 5635527; US 5753670; WO 9533720 .
【2】 Nakamura, N.; Imada, T.; Inoue, Y.; Kosaka, K.; Yoshida, T.; Ono, S.; Fukaya, C.; Maeda, K.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives. Chem Pharm Bull 1999, 47, 12, 1694.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(I)	19581	trans-4-Aminocyclohexanol；trans-4-Amino-1-cyclohexanol;trans-4-Amino-1-cyclohexanol;	27489-62-9	C₆H₁₃NO	详情	详情
(II)	21488	N,N'-dimethylurea	96-31-1	C₃H₈N₂O	详情	详情
(III)	37350	5-(4-hydroxycyclohexyl)-1,3-dimethyl-1,3,5-triazinan-2-one		C₁₁H₂₁N₃O₂	详情	详情
(IV)	37351	tert-butyl 2-[[4-(3,5-dimethyl-4-oxo-1,3,5-triazinan-1-yl)cyclohexyl]oxy]acetate		C₁₇H₃₁N₃O₄	详情	详情
(V)	37352	tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate		C₁₂H₂₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Pinner reaction of ethyl 5-cyano-2-benzofurancarboxylate (VI) gave imidate (VII) and subsequent treatment with ethanolic ammonia afforded amidine (VIII). After basic hydrolysis of the ester group of (VIII), protection with benzyl chloroformate provided the benzyloxycarbonyl derivative (IX). Coupling of (IX) with aminoester (V) in the presence of EDC and HOBt yielded amide (X). Sequential cleavage of benzyloxycarbonyl and tert-butyl groups orf (X) provided amidino acid (XI), which was finally esterified with EtOH and methanesulfonic acid.

参考文献中间体

合成目标

【1】 Ono, S.; Yoshida, T.; Ashimori, A.; Kosaka, K.; Okada, T.; Maeda, K.; Eda, M.; Mori, F.; Inoue, Y.; Ebisu, H.; Imada, T.; Ikegawa, R.; Wang, F.; Nakamura, N. (Welfide Corporation); Novel fused-ring carboxylic acid cpds. or salt thereof,and medicinal use thereof. EP 0712844; JP 1996053398; JP 1996231548; US 5635527; US 5753670; WO 9533720 .
【2】 Nakamura, N.; Imada, T.; Inoue, Y.; Kosaka, K.; Yoshida, T.; Ono, S.; Fukaya, C.; Maeda, K.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives. Chem Pharm Bull 1999, 47, 12, 1694.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(V)	37352	tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate		C₁₂H₂₃NO₃	详情	详情
(VI)	37353	ethyl 5-cyano-1-benzofuran-2-carboxylate		C₁₂H₉NO₃	详情	详情
(VII)	37354	ethyl 5-[ethoxy(imino)methyl]-1-benzofuran-2-carboxylate		C₁₄H₁₅NO₄	详情	详情
(VIII)	37355	ethyl 5-[amino(imino)methyl]-1-benzofuran-2-carboxylate		C₁₂H₁₂N₂O₃	详情	详情
(IX)	37356	5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-carboxylic acid		C₁₈H₁₄N₂O₅	详情	详情
(X)	37357	ethyl 2-([4-[([5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-yl]carbonyl)amino]cyclohexyl]oxy)acetate		C₂₈H₃₁N₃O₇	详情	详情
(XI)	37358	2-([4-[([5-[amino(imino)methyl]-1-benzofuran-2-yl]carbonyl)amino]cyclohexyl]oxy)acetic acid		C₁₈H₂₁N₃O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Pinner reaction of ethyl 5-cyano-2-benzofurancarboxylate (I) gave imidate (II) and subsequent treatment with ethanolic ammonia afforded amidine (III). After basic hydrolysis of the ester group of (III), protection with benzyl chloroformate provided the benzyloxycarbonyl derivative (IV). Coupling of (IV) with ethyl trans-3-(4-aminocyclohexyl)propionate (V) in the presence of EDC and HOBt yielded amide (VI). Finally, hydrogenolysis of the benzyloxycarbonyl protecting group of (VI) provided the title amidino ester.

参考文献中间体

合成目标

【1】 Ono, S.; Yoshida, T.; Ashimori, A.; Kosaka, K.; Okada, T.; Maeda, K.; Eda, M.; Mori, F.; Inoue, Y.; Ebisu, H.; Imada, T.; Ikegawa, R.; Wang, F.; Nakamura, N. (Welfide Corporation); Novel fused-ring carboxylic acid cpds. or salt thereof,and medicinal use thereof. EP 0712844; JP 1996053398; JP 1996231548; US 5635527; US 5753670; WO 9533720 .
【2】 Nakamura, N.; Imada, T.; Inoue, Y.; Kosaka, K.; Yoshida, T.; Ono, S.; Fukaya, C.; Maeda, K.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives. Chem Pharm Bull 1999, 47, 12, 1694.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(I)	37353	ethyl 5-cyano-1-benzofuran-2-carboxylate		C₁₂H₉NO₃	详情	详情
(II)	37354	ethyl 5-[ethoxy(imino)methyl]-1-benzofuran-2-carboxylate		C₁₄H₁₅NO₄	详情	详情
(III)	37355	ethyl 5-[amino(imino)methyl]-1-benzofuran-2-carboxylate		C₁₂H₁₂N₂O₃	详情	详情
(IV)	37356	5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-carboxylic acid		C₁₈H₁₄N₂O₅	详情	详情
(V)	37352	tert-butyl 2-[(4-aminocyclohexyl)oxy]acetate		C₁₂H₂₃NO₃	详情	详情
(VI)	37357	ethyl 2-([4-[([5-[[[(benzyloxy)carbonyl]amino](imino)methyl]-1-benzofuran-2-yl]carbonyl)amino]cyclohexyl]oxy)acetate		C₂₈H₃₁N₃O₇	详情	详情

Extended Information