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Production Example 1 Ethyl 5-methyl-4-oxo-2-(thiophen-3-ylmethyl)-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate 515 Milligrams of diethyl 5-amino-3-methylthiophene-2,4-dicarboxylate and 296 mg of 3-thiopheneacetonitrile were added to 8 mL of 4N hydrogen chloride-dioxane solution and stirred for 10 hours. Thereafter the liquid reaction mixture was poured on ice, and its pH was adjusted to 8 - 9 with 25% aqueous ammonia. Whereupon precipitated crystals were recovered by filtration and washed first with water, and then with hexane. The crude crystals were recrystallized from a liquid mixture of N,N-dimethylformamide and cyclohexane, to provide 397 mg of the title compound. 1H-NMR(DMSO-d6) δ: 1.30(3H,t,J=7, 1Hz),2.81(3H,s), 3.97(2H,s),4.30(2H,q,J=7.1Hz),7.0-7.6(3H,m),12.74(1H,br s) MS(m/z):334(M+) |
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With hydrogenchloride; In 1,4-dioxane; cyclohexane; N,N-dimethyl-formamide; |
1-a : Synthesis of ethyl 5-methyl-4-oxo-2-(thiophen-3-ylmethyl)-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate To 8 mL of 4N hydrogen chloride in dioxane solution, 515 mg of diethyl 5-amino-3-methylthiophene-2,4-dicarboxylate and 296 mg of 3-thiopheneacetonitrile were added, and stirred for 10 hours. Thereafter the liquid reaction mixture was poured on ice, and its pH was adjusted to 8-9 with 25% aqueous ammonia. Whereupon precipitated crystals were recovered by filtration and washed with water and hexane, by the order stated. The crude crystals were recrystallized from a liquid mixture of N,N-dimethylformamide and cyclohexane, to provide 397 mg of the title compound. 1H-NMR(DMSO-d6)δ:1.30(3H,t,J=7.1Hz),2.81(3H,s),3.97(2H,s), 4.30(2H,q,J=7.1Hz),7.0-7.6(3H,m),12.74(1H,br s) MS(m/z):334(M+) |