5-Bromo-2-methyl-4-pyrimidinecarboxylic acid

Step 42a: 5-Bromo-2-methylpyrimidine (Compound 0601-120)Sodium (356 mg, 15.5 mmol) was carefully added to ethanol (5.9 mL) to prepare sodium ethoxide solution in ethanol. The above freshly prepared sodium ethoxide in ethanol solution (3.5 mL) was added to a stirred suspension of acetamidine hydrochloride (0.91 g, 9.69 mmol). The mixture was warmed to 50 °C, then the heating bath was removed and a solution of mucobromic acid (1 g, 3.87 mmol) in ethanol was added dropwise at a rate which maintained a constant temperature, followed by a further sodium ethoxide in ethanol solution (2 mL). After cooling, the mixture was filtered and evaporated to a residue which was shaken vigorously with hydrochloric acid (2 M x 2.4 mL). The brown precipitate was filtered and washed with cold water, then freeze-dried to give 5-bromo-2- methylpyrimidine-4-carboxylic acid (350 mg, 42percent) as a brown solid. LCMS: 218 [M+l]Step 42a: 5-Bromo-2-methylpyrimidine (Compound 0601-120)[0365]Sodium (356 mg, 15.5 mmol) was carefully added to ethanol (5.9 mL) to prepare sodium ethoxide solution in ethanol. The above freshly prepared sodium ethoxide in ethanol solution (3.5 mL) was added to a stirred suspension of acetamidine hydrochloride (0.91 g, 9.69 mmol). The mixture was warmed to 50° C., then the heating bath was removed and a solution of mucobromic acid (1 g, 3.87 mmol) in ethanol was added dropwise at a rate which maintained a constant temperature, followed by a further sodium ethoxide in ethanol solution (2 mL). After cooling, the mixture was filtered and evaporated to a residue which was shaken vigorously with hydrochloric acid (2 M×2.4 mL). The brown precipitate was filtered and washed with cold water, then freeze-dried to give 5-bromo-2-methylpyrimidine-4-carboxylic acid (350 mg, 42percent) as a brown solid. LCMS: 218 [M+1]Sodium (356mg, 15.5mmol) was added to the carefully ethanol (5.9mL), and in ethanolSodium ethoxide solution was prepared. Sodium ethoxide in freshly prepared ethanol solution of the above (3.5 mL) was added to a stirred suspension of acetamidine hydrochloride (0.91g, 9.69mmol). The mixture was allowed to warm up to 50 , and then the heating bath was removed, Mukoburomu acid (1g, 3.87mmol) a solution in ethanol, was dropped so that a constant temperature is maintained, then further, ethanol solution (2mL) sodium ethoxide was dropped of. After cooling, the mixture was filtered, and the residue was evaporated, stirred vigorously with hydrochloric acid (2Mx2.4mL). The brown precipitate was filtered, washed with cold water, and then to obtain a freeze-dried to give 5-bromo-2-methyl-pyrimidine-4-carboxylic acid (350mg, 42percent) as a brown solid.To a solution of the commercially available ethanimidamide ii, ashydrochloride, (6.0 g, 63.83 mmol) in anhydrous EtOH (20 mL) was added sodium ethoxide (20 mL of a 2i percent solution in ethanol) and the reactionmixture was stirred at 50 00 and the commercially available (2E)-2, 3-dibromo-4-oxobut-2-enoic acid i 2 (6.82 g, 26.74 mmol) in EtOH (i 0 mL) was added into the mixture. After stirring at 50 00 for i hour, a further portion of sodiumethoxide (i 0 mL of a 2i percent solution in ethanol) was added and the mixture was stirred at r.t. for i6 h. The reaction mixture was filtrated and the filtratereduced in vacuo. The residue was then treated with 2 M aqueoushydrochloric acid (30 mL) and stirred vigorously for 30 mm. The resulting solid was filtrated, washed with water and air dried to give KR-i 3 (i .46 g, 25.2percent) as a pale yellow solid. ESI-MS (M+i): 2i7 calc. for C6H5BrN2O2:2i6.0.General procedure: To a solution of Intermediate 7 (110 mg, 0.37 mmol), 3-methoxybenzene-1, 2- diamine (50 mg, 0.34 mmol) and DIPEA (0.2 mL, 1 mmol) in DMF (2 mL) was added HATU (160 mg, 0.41 mmol). The reaction mixture was stirred at r.t. for 48 h, then partitioned between DCM and water. The organic phase was separated, then dried and concentrated in vacuo. The crude residue was purified by flash column chromatography (0-100% EtOAc/hexanes) to give the title compound (28.7 mg, 20%) as a white solid. LCMS (Method 5): [M+H]+ m/z 415, RT 1.31 minutes.To a solution of the commercially available ethanimidamide ii, ashydrochloride, (6.0 g, 63.83 mmol) in anhydrous EtOH (20 mL) was added sodium ethoxide (20 mL of a 2i % solution in ethanol) and the reactionmixture was stirred at 50 00 and the commercially available (2E)-2, 3-dibromo-4-oxobut-2-enoic acid i 2 (6.82 g, 26.74 mmol) in EtOH (i 0 mL) was added into the mixture. After stirring at 50 00 for i hour, a further portion of sodiumethoxide (i 0 mL of a 2i % solution in ethanol) was added and the mixture was stirred at r.t. for i6 h. The reaction mixture was filtrated and the filtratereduced in vacuo. The residue was then treated with 2 M aqueoushydrochloric acid (30 mL) and stirred vigorously for 30 mm. The resulting solid was filtrated, washed with water and air dried to give KR-i 3 (i .46 g, 25.2%) as a pale yellow solid. ESI-MS (M+i): 2i7 calc. for C6H5BrN2O2:2i6.0.

Molecular Weight:217.02
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:215.95344
Monoisotopic Mass:215.95344
Topological Polar Surface Area:63.1
Heavy Atom Count:11
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes