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【结 构 式】

【分子编号】31662

【品名】4-(hydroxymethyl)-2-thiophenecarbonitrile

【CA登记号】

【 分 子 式 】C6H5NOS

【 分 子 量 】139.17784

【元素组成】C 51.78% H 3.62% N 10.06% O 11.5% S 23.04%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(III)

The reduction of 5-bromothiophene-3-carbaldehyde (I) with NaBH4 in THF gives the corresponding carbinol (II), which is treated with Zn(CN)2 and palladium tetrakis(triphenylphosphine) in DMF to yield 4-(hydroxymethyl)thiophene-2-carbonitrile (III). The reaction of (III) with tetrabromomethane and triphenylphosphine affords the corresponding bromomethyl derivative (IV), which is condensed with 3(S)-(tert-butoxycarbonylamino)pyrrolidin-2-one (V) by means of NaH in THF/DMF to give the expected addition product (VI). The deprotection of the amino group of (VI) with HCl in ethyl acetate yields the primary amine (VII), which is acylated with 7-methoxynaphthalene-2-sulfonyl chloride (VIII) and triethylamine in dichloromethane providing the sulfonamide (IX). The methylation of (IX) with methyl iodide and K2CO3 in DMF affords the N-methylsulfonamide (X), which is finally treated first with HCl in ethanol, and then with NH3 in methanol to convert the cyano group of (X) into the amidino group of the target compound.

1 Ewing, W.R.; Manetta, V.E.; Becker, M.R.; et al.; Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa. J Med Chem 1999, 42, 18, 3557.
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) 31660 5-bromo-3-thiophenecarbaldehyde C5H3BrOS 详情 详情
(II) 31661 (5-bromo-3-thienyl)methanol C5H5BrOS 详情 详情
(III) 31662 4-(hydroxymethyl)-2-thiophenecarbonitrile C6H5NOS 详情 详情
(IV) 31663 4-(bromomethyl)-2-thiophenecarbonitrile C6H4BrNS 详情 详情
(V) 29492 tert-butyl (3S)-2-oxopyrrolidinylcarbamate C9H16N2O3 详情 详情
(VI) 31664 tert-butyl (3S)-1-[(5-cyano-3-thienyl)methyl]-2-oxopyrrolidinylcarbamate C15H19N3O3S 详情 详情
(VII) 31665 4-[[(3S)-3-amino-2-oxopyrrolidinyl]methyl]-2-thiophenecarbonitrile C10H11N3OS 详情 详情
(VIII) 31666 7-methoxy-2-naphthalenesulfonyl chloride C11H9ClO3S 详情 详情
(IX) 31667 N-[(3S)-1-[(5-cyano-3-thienyl)methyl]-2-oxopyrrolidinyl]-7-methoxy-2-naphthalenesulfonamide C21H19N3O4S2 详情 详情
(X) 31668 N-[(3S)-1-[(5-cyano-3-thienyl)methyl]-2-oxopyrrolidinyl]-7-methoxy-N-methyl-2-naphthalenesulfonamide C22H21N3O4S2 详情 详情
Extended Information