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【结 构 式】 
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【分子编号】32410 【品名】methyl 3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxylate 【CA登记号】 |
【 分 子 式 】C14H12N6O3 【 分 子 量 】312.28792 【元素组成】C 53.85% H 3.87% N 26.91% O 15.37% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 2-(bromomethyl)acrylic acid methyl ester (I) with 1H-tetrazole (II) by means of K2CO3 in DMF gives 2-(1-tetrazolylmethyl)acrylic acid methyl ester (III), which is cyclized with 3-cyanobenzaldehyde oxime (IV) by means of NaOCl yielding the oxazoline carboxylic ester (V). The hydrolysis of (V) with LiOH in THF affords the free carboxylic acid (VI), which is condensed with 2-(6-aminopyridin-3-yl)-N-tert-butybenzenesulfonamide (VII) by means of SOCl2 and triethylamine giving the carboxamide (VIII). Finally, this compound is treated with HCl and then with ammonium acetate to eliminate the tert-butyl protecting group and to hydrolyze the cyano group to the target amidino compound.
| 【1】 Alexander, R.S.; Wesler, R.R.; Ellis, C.D.; Quan, M.L.; Liauw, A.Y.; Wong, P.C.; Lam, G.; Knabb, R.M.; Wright, M.R.; Design and synthesis of isoxazoline derivatives as factor Xa inhibitors. 2(1). J Med Chem 1999, 42, 15, 2760. |
| 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) | 32407 | methyl 2-(bromomethyl)acrylate | C5H7BrO2 | 详情 | 详情 | |
| (II) | 32408 | 1H-1,2,3,4-tetraazole; Tetrazole | 288-94-8 | CH2N4 | 详情 | 详情 |
| (III) | 32409 | methyl 2-(1H-1,2,3,4-tetraazol-1-ylmethyl)acrylate | C6H8N4O2 | 详情 | 详情 | |
| (IV) | 23357 | 3-[(hydroxyimino)methyl]benzonitrile | C8H6N2O | 详情 | 详情 | |
| (V) | 32410 | methyl 3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxylate | C14H12N6O3 | 详情 | 详情 | |
| (VI) | 32411 | 3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxylic acid | C13H10N6O3 | 详情 | 详情 | |
| (VII) | 32412 | 2-(6-amino-3-pyridinyl)-N-(tert-butyl)benzenesulfonamide | C15H19N3O2S | 详情 | 详情 | |
| (VIII) | 32413 | N-(5-[2-[(tert-butylamino)sulfonyl]phenyl]-2-pyridinyl)-3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxamide | C28H27N9O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The condensation of 2-(bromomethyl)acrylic acid methyl ester (I) with 1H-tetrazole (II) by means of K2CO3 in DMF gives 2-(1-tetrazolylmethyl)acrylic acid methyl ester (III), which is cyclized with 3-cyanobenzaldehyde oxime (IV) by means of NaOCl yielding the oxazoline carboxylic ester (V). The hydrolysis of (V) with LiOH in THF affords the free carboxylic acid (VI), which is condensed with 4'-amino-N-tert-butylbiphenyl-2-sulfonamide (VII) by means of SOCl2 and triethylamine giving the carboxamide (VIII). Finally, this compound is treated with HCl and then with ammonium acetate to eliminate the tert-butyl protecting group and to hydrolyze the cyano group to the target amidino compound.
| 【1】 Alexander, R.S.; Wesler, R.R.; Ellis, C.D.; Quan, M.L.; Liauw, A.Y.; Wong, P.C.; Lam, G.; Knabb, R.M.; Wright, M.R.; Design and synthesis of isoxazoline derivatives as factor Xa inhibitors. 2(1). J Med Chem 1999, 42, 15, 2760. |
| 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) | 32407 | methyl 2-(bromomethyl)acrylate | C5H7BrO2 | 详情 | 详情 | |
| (II) | 32408 | 1H-1,2,3,4-tetraazole; Tetrazole | 288-94-8 | CH2N4 | 详情 | 详情 |
| (III) | 32409 | methyl 2-(1H-1,2,3,4-tetraazol-1-ylmethyl)acrylate | C6H8N4O2 | 详情 | 详情 | |
| (IV) | 23357 | 3-[(hydroxyimino)methyl]benzonitrile | C8H6N2O | 详情 | 详情 | |
| (V) | 32410 | methyl 3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxylate | C14H12N6O3 | 详情 | 详情 | |
| (VI) | 32411 | 3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxylic acid | C13H10N6O3 | 详情 | 详情 | |
| (VII) | 23363 | 4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide | C16H20N2O2S | 详情 | 详情 | |
| (VIII) | 32414 | N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-3-(3-cyanophenyl)-5-(1H-1,2,3,4-tetraazol-1-ylmethyl)-4,5-dihydro-5-isoxazolecarboxamide | C29H28N8O4S | 详情 | 详情 |