Syntheses, Crystal Structures, and Antitumor Activities of Two 2-Trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]-thieno[2,3-d]pyrimidin-4-amine Derivatives

Abstract

Two novel 2-trifluoromethyl-5,6,7,8-tetrahydrobenzo(4,5)thieno(2,3-d)pyrimidin-4- amine derivatives were synthesized by nucleophilic substitution of two appropriate amines with 4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydrobenzothieno(2,3-d)pyrimidine, which started from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carbonitrile, trifluoroacetic acid (TFA) and phosphorous oxychloride by one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Compound 1, N-(furan-2-ylmethyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzo- thieno(2,3-d)pyrimidin-4-amine, crystallizes in the monoclinic system, space group C2/c with a = 26.352(3), b = 7.5991(8), c = 17.1423(18) A, β = 114.667(2)°, V = 3119.5(6) A 3 and Z = 8. Compound 2, N-(3-silatranylpropyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno(2,3-d)pyri- midin-4-amine, crystallizes in the monoclinic system, space group P21/n with a = 13.4394(13), b = 8.9446(9), c = 18.9657(18) A, β = 101.9640(10)°, V = 2230.3(4) A 3 and Z = 4. The preliminary bioassay indicated that compound 2 exhibits more potent antitumor activity against BCG-823 than 5-fluorouracil (5-FU).