4-CHLORO-2-METHYL-5,6,7,8-TETRAHYDRO[1]BENZOTHIENO[2,3-D]PYRIMIDINE

General procedure: The different thieno[2, 3-d]pyrimidin-4-one (6a-d or f-i) (1 eq.) and phosphoryl chloride (2.9 mL/mmoleq.) were refluxed for 8 h. The reaction mixture was then cooled in an ice-bath and carefully neutralised by the addition of aqueous saturated NaHCO3 solution. The resulting mixture was extracted with ethylacetate (15 mL/mmol eq.), the organic layer was separated, dried over MgSO4 and concentrated. The crude residue was purified by flash column chromatography eluting with n-hexane-EtOAc 100:0 v/vincreasing to n-hexane-EtOAc 85:15 v/v unless otherwise stated.General procedure: The different thieno[2, 3-d]pyrimidin-4-one (6a-d or f-i) (1 eq.) and phosphoryl chloride (2.9 mL/mmoleq.) were refluxed for 8 h. The reaction mixture was then cooled in an ice-bath and carefully neutralised by the addition of aqueous saturated NaHCO3 solution. The resulting mixture was extracted with ethylacetate (15 mL/mmol eq.), the organic layer was separated, dried over MgSO4 and concentrated. The crude residue was purified by flash column chromatography eluting with n-hexane-EtOAc 100:0 v/vincreasing to n-hexane-EtOAc 85:15 v/v unless otherwise stated.General procedure: To a solution of compound 4 (0.65 mmol) or compound 27, compound 5 (0.73 mmol) and sodium bicarbonate (1.30 mmol) in DMSO (5 mL) was stirred at 80 C for 16 h. The mixture was extracted with ethyl acetate. The extract was washed with saline and the solvents were removed in vacuo. The crude product was purified by silica gel chromatography using cyclohexane-ethyl acetate(25:1) as eluate to give compound 6-13 or compound 28 (63% yield) as white solid. 2-Methyl-4-((1-phenyl-1H-tetrazol-5-yl)thio)-5, 6, 7, 8-tetrahydrobenzo [4, 5]thieno[2, 3-d]pyrimidine (6). Yield=36%; 1H NMR (500 MHz, CDCl3) delta 7.63 (dt, J=8.4, 3.6 Hz, 2H), 7.55-7.44 (m, 3H), 3.04 (t, J=4.8 Hz, 2H), 2.86 (d, J=5.2 Hz, 2H), 2.45 (s, 3H), 1.99-1.88 (m, 4H), 1.28 (s, 1H). 13C NMR (126 MHz, CDCl3) delta 167.74 (s), 161.14 (s), 155.98 (s), 146.50 (s), 137.61 (s), 134.23 (s), 130.44 (s), 129.40 (s), 125.90 (d, J=14.9 Hz), 124.53 (s), 29.70 (s), 26.07 (s), 25.72 (s), 25.21 (s), 22.42 (d, J=12.8 Hz). ESI-MS m/z: 381.2 [M+H]+.General procedure: The different thieno[2, 3-d]pyrimidin-4-one (6a-d or f-i) (1 eq.) and phosphoryl chloride (2.9 mL/mmoleq.) were refluxed for 8 h. The reaction mixture was then cooled in an ice-bath and carefully neutralised by the addition of aqueous saturated NaHCO3 solution. The resulting mixture was extracted with ethylacetate (15 mL/mmol eq.), the organic layer was separated, dried over MgSO4 and concentrated. The crude residue was purified by flash column chromatography eluting with n-hexane-EtOAc 100:0 v/vincreasing to n-hexane-EtOAc 85:15 v/v unless otherwise stated.

Molecular Weight:238.74
XLogP3:4.1
Hydrogen Bond Acceptor Count:3
Exact Mass:238.0331472
Monoisotopic Mass:238.0331472
Topological Polar Surface Area:54
Heavy Atom Count:15
Complexity:251
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes