【药物名称】Iclaprim, AR-101((R)-isomer), AR-102((S)-isomer), RO-48-2622, AR-100
化学结构式(Chemical Structure):
参考文献No.33557
标题:Diaminopyrimidines, pharmaceutical compsns. containing them and their use as antibacterial
作者:Masciadri, R. (F. Hoffmann-La Roche AG)
来源:EP 0866791; JP 2000501399; US 5773446; WO 9720839
合成路线图解说明:

The reaction of cyclopropanecarbonyl chloride (I) with bis(trimethylsilyl)acetylene (II) gives 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one (III), which is reduced with NaBH4 and CeCl3 in methanol to the corresponding propynol (IV). The condensation of (IV) with 3-hydroxy-4,5-dimethoxybenzaldehyde (V) by means of triphenylphosphine and dimethyl azodicarboxylate in toluene yields the expected propynyl ether (VI), which is cyclized in N,N-diethylaniline at 200 C affording 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carbaldehyde (VII). The condensation of (VII) with 3-anilinopropionitrile (VIII) by means of potassium tert-butoxide in DMSO gives the acrylonitrile (IX), which is finally cyclized with guanidine (X) by means of potassium tert-butoxide in ethanol. (1)

合成路线图解说明:

The reaction of cyclopropanecarbonyl chloride (I) with bis(trimethylsilyl)acetylene (II) gives 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one (III), which is reduced with NaBH4 and CeCl3 in methanol to the corresponding propynol (IV). The condensation of propynol (IV) with 3-hydroxy-4,5-dimethoxybenzoic acid methyl ester (XI) by means of triphenylphosphine and dimethyl azodicarboxylate in toluene yields the expected propynyl ether (XII), which is cyclized in N,N-diethylaniline at 200 C affording 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carboxylic acid methyl ester (XIII). Finally, this compound is reduced with NaAlH2(OCH2CH2)2 and morpholine in toluene to give the previously described 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carbaldehyde (VII). The condensation of (VII) with 3-anilinopropionitrile (VIII) by means of potassium tert-butoxide in DMSO gives the acrylonitrile (IX), which is finally cyclized with guanidine (X) by means of potassium tert-butoxide in ethanol.

参考文献No.785046
标题:Iclaprim
作者:Sorbera, L.A.; Casta馿r, J.; Rabasseda, X.
来源:Drugs Fut 2004,29(3),220
合成路线图解说明:

The reaction of cyclopropanecarbonyl chloride (I) with bis(trimethylsilyl)acetylene (II) gives 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one (III), which is reduced with NaBH4 and CeCl3 in methanol to the corresponding propynol (IV). The condensation of (IV) with 3-hydroxy-4,5-dimethoxybenzaldehyde (V) by means of triphenylphosphine and dimethyl azodicarboxylate in toluene yields the expected propynyl ether (VI), which is cyclized in N,N-diethylaniline at 200 C affording 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carbaldehyde (VII). The condensation of (VII) with 3-anilinopropionitrile (VIII) by means of potassium tert-butoxide in DMSO gives the acrylonitrile (IX), which is finally cyclized with guanidine (X) by means of potassium tert-butoxide in ethanol. (1)

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