2-Methyl-4-pyrimidinecarboxylic acid

A mixture of 3-((6-aminopyridin-3-yl)methyl)-5-fluorobenzonitrile (227 mg, 1 .0 mmol), To a solution of 5-(3-chlorobenzyl)pyridin-2-amine (0.132 g, 0.6 mmol), To a solution of 5-((6-aminopyridin-3-yl)methyl)-2-fluorobenzonitrile (0.227 mg, 1 .0 mmol), In a 40 ml_ reaction vial, combined 5-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)pyridin-2-amine (0.500 g, 2.27 mmol), dipotassium carbonate (0.375 g, 2.72 mmol) and A2-iron(2+) b/'s((cyclopenta-2, 4-diyn-1 -yl)diphenyl-A4-phosphane) palladium dichloride (0.082 g, 0.1 135 mmol). Added 1 , 4-dioxane (6 ml_) and water (2 ml_) and added 1 -(bromomethyl)-3-fluorobenzene (278 mI_, 2.27 mmol). The reaction was degassed by cycling with vacuum and nitrogen gas for 3 cycles. Stirred the reaction at 80 C for 16 h. Cooled to room temperature and diluted with ethyl acetate (15 ml_), then washed with water (10 ml_), then brine (10 ml_). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purified reaction by column chromatography (eluting with 0-100% ethyl acetate/hexanes through 24 g of silica gel) to give 5-[(3-fluorophenyl)methyl]pyridin-2-amine as a brown solid (131 mg, 0.648 mmol, 28%). 1 H NMR (300 MHz, Chloroform-d) d 8.02 - 7.94 (m, 1 H), 7.33 - 7.18 (m, 2H), 7.06 - 6.80 (m, 3H), 6.47 (dd, J = 8.4, 0.9 Hz, 1 H), 4.36 (s, 2H), 3.84 (s, 2H).To a solution of 2-methylpyrimidine-5-carboxylic acid (100 mg, 0.724 mmol) and diisopropylethylamine (281 mg, 2.17 mmol) in tetrahydrofuran (4 ml_) at 20 C was added 1 -[b/'s(dimethylamino)methylene]- 1H- 1 , 2, 3-triazolo[4, 5-b]pyridinium 3-oxid hexafluorophosphate (413 mg, 1 .09 mmol). The reaction mixture was stirred for 20 minutes before a solution of 5-(3-fluorobenzyl)pyridin-2-amine (146 mg, 0.724 mmol) in tetrahydrofuran (1 .0 ml_) was added. The reacton solution was heated to 90 C and stirred at 90 C for 1 h. The volatiles were removed under reduced pressure and the residue was added to a mixture of dichloromethane (50 ml_) and water (50 ml_). The organic layer was collected, dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (silica gel, dichloromethane/methanol = 20/1 ) to offer A/-(5-(3-fluorobenzyl)pyridin-2-yl)-2-methylpyrimidine-5-carboxamide (93.1 mg, 0.29 mmol, 40%) as a white solid. 1 H NMR (400 MHz, Dimethylsulfoxide-c/6) d 1 1 .19 (s, 1 H), 9.18(s, 2H), 8.34 (d, J = 2.0 Hz, 1 H), 8.12 (d, J = 8.8 Hz, 1 H), 7.73-7.76 (m, 1 H), 7.33-7.38 (m, 1 H), 7.02-7.14 (m, 3H), 3.99 (s, 2H), 2.70 (s, 3H); LCMS (ESI) m/z: 323.1 [M+H]+. (250 mg, 1.810 mmol) was slurried in N, N, Dimethylformamide (dry) (3 ml). DIPEA (0.378 ml, 2.172 mmol) was added followed by HATU (757 mg, 1.991 mmol). After 15 mins 2-chloroaniline (0.191 ml, 1.810 mmol) was added to the brown suspension and the resulting reaction mixture stirred further at room temperature overnight. The reaction mixture was evaporated (55C to half volume (~4ml). This mixture was added to a cold water/ sat. sodium bicarbonate mixture (2:1, 20 ml). The solvents were filtered and the residue was taken in DCM. The organic layer was dried with Na2SO4, filtered and the filtrate was evaporated to dryness to give the product as a beige solid. Used as such.

Molecular Weight:138.12
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:138.042927438
Monoisotopic Mass:138.042927438
Topological Polar Surface Area:63.1
Heavy Atom Count:10
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes