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Two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine,which started from 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile,trifluoroacetic acid(TFA) and phosphoryl trichloride via one-pot procedure.Their structures were determined by single-crystal X-ray diffraction.Enantiomer(R)-3,(R)-N-(1-phenylethyl)-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system,space group P4_3 with a = 8.6847(6),b = 8.6847(6),c = 22.419(2) A,V= 1690.9(3) A~3,Z = 4,D_c =1.428 g/cm~3,μ = 0.228 mm~(-1),F(000) = 752,the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with I > 2σ(I).Enantiomer(S)-3,(S)-N-(1-phenylethyl)-2-trifluoromethyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-amine crystallizes in the tetragonal system,space group P4_1 with a = 8.688,b = 8.688,c = 22.421 A,V = 1692.4 A~3,Z = 4,D_c = 1.426 g/cm~3,μ = 0.227mm~(-1),F(000) = 752,the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with I >2σ(I).The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib.
Synthesis of two enantiomeric 2-trifluoromethyl-6,7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d] pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two chiral amines with 4-chloro-2- trifluoromethyl-6,7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d] pyrimidine, which started from 2-amino-5,6-dihydro-4H-cyclopenta [b] thiophene-3-carbonitrile , trifluoroacetic acid (TFA) and phosphoryl trichloride via one-pot procedure. Their structures were determined by single-crystal X- ray diffraction. Enantiomer (R) -3, Pyrimidin-4-amine crystallizes in the tetragonal system, space group P4_3 with a = 8.6847 (6), b = 8.6847 (6) , C = 22.419 (2) A, V = 1690.9 (3) A~3, Z = 4, D_c = 1.428 g / cm~3, μ = 0.228 mm -1, F 000 = 752, the final R = 0.0463 and wR = 0.1257 for 3442 observed reflections with I> 2σ (I) .Enantiomer (S) -3, (S) -N- 5H-cyclopenta [4,5] thieno [2,3-d] pyrimidin-4-amine crystallizes in the t etragonal system, space group P4_1 with a = 8.688, b = 8.688, c = 22.421 A, V = 1692.4 A -3, Z = 4, D c = 1.426 g / cm 3, μ = 0.227 mm -1, F (000) = 752, the final R = 0.0682 and wR = 0.1806 for 3182 observed reflections with I> 2σ (I). The preliminary bioassay indicated that the R-enantiomer exhibits higher antitumor activity against MCF-7 than gefitinib.