7-BROMOTHIENO[3,2-D]PYRIMIDIN-4(1H)-ONE

A dilution of bromine (40.4 mL, 0.78 mol) in acetic acid (122 mL, 2.1 mol) was slowly added to a solution of thieno[3, 2-d]pyrimidin-4(3H)-one (38.0 g, 0.25 mol) in acetic acid (143 mL, 2.5 mol). With the reactor closed, the reaction mixture was stirred at 120°C for 18 hrs. After the reaction mixture was cooled to room temperature, it was subjected to vacuum distillation to remove acetic acid therefrom. The concentrate was poured into ice water to form precipitates, which were filtered and dried to obtain the desired compound without further purification (37.5 g, 65percent). 'H-NMR(300MHz, DMSO-dThieno[3, 2-d]pyrimidin-4(3H)-one (38.0 g, 0.25 mol) was dissolved in acetic acid (143 mL, 2.5 mol), and bromine (40.4 mL, 0.78 mol) diluted with acetic acid (122 mL, 2.1 mol) was slowly added to the solution prepared. The reaction solution was stirred in a sealed reactor for 18 hours at 120° C. The reaction solution was cooled to room temperature and acetic acid was removed by distillation under reduced pressure. The reaction mixture was poured into an ice water to generate a solid compound, and the resulting solid compound was filtered and dried. The title compound was obtained without purification (37.5 g, 65percent). 7-Bromo-3H-thieno[3, 2-d]pyrimid-4-one (191): To a solution of 3H-thieno[3, 2-d]pyrimid-4-one (190, 0.98 g, 6.40 mmol) in acetic acid (3.4 mL) was added a solution of bromine (1 mL) in acetic acid (3 mL). The reaction mixture was heated at reflux for 8 hours. The resulting suspension was allowed to cool to room temperature and then poured into a saturated aqueous solution of sodium bicarbonate to neutralize. The solid product was collected by vacuum filtration to give 7-bromo-3H-thieno[3, 2-d]pyrimid-4-one (0.94 g, 64percent yield) as a pale yellow solid.To a solution of 3//-thieno[3, 2-d]Dulfona-4-one (25 g, 164 mmol) in acetic acid(200 mL) was added bromine (26 mL) dropwise. The reaction mixture was heated at 100 Thieno[3, 2-d]pyrimidin-4(3H)-one (12.5 g) was dissolved in acetic acid (52 mL), and bromine (13 mL) was added thereto. The reaction mixture was stirred at 120° C. for 12 hours in a hermetically sealed reactor. The reaction mixture was cooled to room temperature and distilled under reduced pressure to remove acetic acid. The reaction mixture was placed in ice water, and the solid thus obtained was filtered and washed with ether, and dried to obtain the title compound (7.8 g). [0172] Step 2: Thieno[3, 2-d]pyrimidin-4(3H)-one (12.5 g) was dissolved in acetic acid (52 mL), and bromine (13 mL) was added thereto. The resulting mixture was stirred in a sealed container for 12 hrs at 120° C., cooled down to room temperature, and purified by distillation under reduced pressure to remove acetic acid. Ice water was added to the mixture, and a solid thus obtained was washed with ether and dried to obtain the title compound (7.8 g). [0120] To a solution of 3H-thieno[3, 2-d]pyrimid-4-one (82, 0.98 g, 6.4 mmol) in acetic acid (3.4 mL) was added a solution of bromine (1 mL) in acetic acid (3 mL). To a solution of ammonium formate (9.4 g, 0.15 mol) in formamide (14 mL) at 150° C. was added 3-(formylamino)-2-thiophenecarboxylic acid methyl ester (81, 5.2 g, 28 mmol) as a solid in small portions. To a mixture of concentrated hydrobromic acid (1 mL) at 0°C was added compound 12 (350mg, 2.09 mmol) till clear solution obtained. Sodium nitrite (144 mg, 2.09 mmol dissolved in 0.2 mL) was added dropwise and reaction mixture was stirred for 30 min at 0°C. To a separate flask, CuBr (300 mg, 2.09 mmol) and HBr (1 mL) was stirred at 90°C. The first solution was added into the hot solution dropwise, and allowed to heat at 90°C for 2 h. The reaction mixture was brought to RT and quenched with water and extracted in ethyl acetate (3 x 10 mL). The combined organic extracts were washed with brine, dried (Na