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【结 构 式】

【分子编号】17645

【品名】N'-(2-amino-4,6-dichloro-5-pyrimidinyl)-N,N-dimethyliminoformamide

【CA登记号】

【 分 子 式 】C7H9Cl2N5

【 分 子 量 】234.08756

【元素组成】C 35.92% H 3.88% Cl 30.29% N 29.92%

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:(IV)

1) The reaction of 4,6-dihydroxypyrimidine-2,5-diamine (I) with (chloromethylene)dimethylammonium chloride (II) in refluxing chloroform gives 4,6-dichloro-2,5-bis(dimethylaminomethyleneamino)pyrimidine (III), which by reaction with aqueous HCl in hot ethanol yields monoamine (IV). The reaction of (IV) with a refluxing phosphate buffer (pH 3.2) affords N-(2-amino-4,6-dichloropyrimidin-5-yl)formamide (V). The condensation of (V) with (1S,4R)-4-amino-2-cyclopentene-1-methanol (VI) (which was obtained by optical resolution of the cis-racemate (VII) with D-dibenzoyltartaric acid, and elimination of the acid with ion exchange resin Amberlite IA-400, by means of triethylamine and NaOH in refluxing ethanol) gives N-[2-amino-4-chloro-6-[4(S)-(hydroxymethyl)-2-cyclopenten-1(R)-ylamino]pyrimidin-5-yl]formamide (VIII). The cyclization of (VIII) with refluxing diethoxymethyl acetate or triethyl orthoformate yields the corresponding purine derivative (IX), which is finally treated with cyclopropylamine (X) in refluxing n-butanol. 2) The formylation of N-(5-amino-4,6-dichloropyrimidin-2-yl)acetamide (XI) with 95% formic acid in acetic anhydride gives the expected formamide (XII), which is condensed with (1S,4R)-4-amino-2-cyclopentene-1-methanol (VI) by means of triethylamine in hot ethanol to yield the substituted pyrimidine (XIII). Finally, the cyclization of (XIII) with diethoxymethyl acetate as before affords the purine intermediate (IX).

1 Graul, A.; Castaner, J.; Leeson, P.A.; Abacavir Sulfate. Drugs Fut 1998, 23, 11, 1155-1167.
2 Daluge, S.M. (Glaxo Wellcome plc); Therapeutic nucleosides. EP 0434450; JP 1996092252; JP 1999158160; JP 1999343292 .
3 Daluge, S.M. (Glaxo Wellcome plc); Therapeutic nucleosides. AU 8937025; EP 0349242; JP 1990045486; JP 1999139976; US 5034394; US 5089500 .
4 Daluge, S.M.; Martin, M.T.; Fugett, M.J.F.; Chloropyrimide intermediates. WO 9521161 .
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) 17642 2,5-diamino-4,6-pyrimidinediol C4H6N4O2 详情 详情
(II) 17643 (Chloromethylene)dimethylammonium chloride; N-(chloromethylene)-N-methylmethanaminium chloride 3724-43-4 C3H7Cl2N 详情 详情
(III) 17644 N'-(4,6-dichloro-2-[[(E)-(dimethylamino)methylidene]amino]-5-pyrimidinyl)-N,N-dimethyliminoformamide C10H14Cl2N6 详情 详情
(IV) 17645 N'-(2-amino-4,6-dichloro-5-pyrimidinyl)-N,N-dimethyliminoformamide C7H9Cl2N5 详情 详情
(V) 17646 2-amino-4,6-dichloro-5-pyrimidinylformamide C5H4Cl2N4O 详情 详情
(VI) 17647 [(1S,4R)-4-amino-2-cyclopenten-1-yl]methanol C6H11NO 详情 详情
(VII) 63843 (rac)-[(1R*,4S*)-4-amino-2-cyclopenten-1-yl]methanol C6H11NO 详情 详情
(VIII) 17649 2-amino-4-chloro-6-[[(1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-yl]amino]-5-pyrimidinylformamide C11H14ClN5O2 详情 详情
(IX) 17650 [(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol C11H12ClN5O 详情 详情
(X) 12263 Cyclopropylamine; Cyclopropanamine 765-30-0 C3H7N 详情 详情
(XI) 17652 N-(5-amino-4,6-dichloro-2-pyrimidinyl)acetamide C6H6Cl2N4O 详情 详情
(XII) 17653 N-[4,6-dichloro-5-(formylamino)-2-pyrimidinyl]acetamide C7H6Cl2N4O2 详情 详情
(XIII) 17654 N-(4-chloro-5-(formylamino)-6-[[(1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-yl]amino]-2-pyrimidinyl)acetamide C13H16ClN5O3 详情 详情
Extended Information