4-(AMINOMETHYL)-PYRIMIDINE

General procedure: N, N-Diisopropylethylamine (3.0-4.0 eq) was added to 8-methoxyquinoline-3-carboxylic acid (1.0 eq) in solvent (dichloromethane, tetrahydrofuran, or N, N-dimethylformamide, 0.05 to 0.2 M) at room temperature. Then, 1-((dimethylamino)(dimethyliminio)methyl)-1H-[1, 2, 3]triazolo[4, 5-b]pyridine 3-oxide hexafluorophosphate(V)(1.0-1.5 eq) was added and the reaction mixture was stirred for five minutes. Then, amine (1.0 - 2.0 eq) was added and the reaction mixture was stirred for one to sixteen hours. 10% Aqueous citric acid was added and the reaction mixture was extracted with dichloromethane, washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified by RP HPLC or silica gel chromatography to give the quinoline-3-carboxamide (1%-95% yield).4-Bromo-N-(4-ethylphenyl)-N-isobutyl-3-(S-methylsulfonimidoyl)benzenesulfonamide (50.0 mg; 0.11 mmol) and General procedure: To a stirring solution of 2-{2-[(1H-1, 3-benzodiazol-2-ylmethyl)[(tert-butoxy)carbonyl]amino]ethyl}-1, 3- thiazole-4-carboxylic acid (8) (3 g, 7.08 mmol), 1-(pyridin-2-yl)methanamine (1.1 ml, 10.62 mmol), DIPEA (3.7 ml, 21.24 mmol) and DMF (50 ml) at room temperature was added HATU (5.39 g, 14.16 mmol). The reaction mixture was allowed to stir at room temperature for 16 h. The reaction was diluted with EtOAc (100 ml) and washed with sat. NaHCQ (3 x 50 ml) and brine (3 x 50 ml). The organic layer was separated, dried (MgS04), filtered and evaporated to dryness. The crude residue was purified by flash column chromatography (kp-NH, eluting with a gradient of 20-100% EtOAc in heptane) and then azeotroped with heptane to give the title compound (2.2 g, 62%) as a yellow foam. 1H-NMR (MeOD, 500 MHz): d[ppm]= 8.49 (d, J = 4.4 Hz, 1H), 8.10 (s, 1H), 7.80 (td, J = 7.8, 1.7 Hz, 1H), 7.54 (s, 2H), 7.42 (d, J = 7.9 Hz, 1H), 7.31 (dd, J = 7.1, 5.2 Hz, 1H), 7.26- 7.20 (m, 2H), 4.75 (d, J = 12.3 Hz, 2H), 4.70 (s, 2H), 3.92-3.79 (m, 2H), 3.36 (d, J = 8.1 Hz, 1H), 1.43- 1.25 (m, 10H) HPLCMS (Method D): [m/z]: 493.1 [M+H]+In a similar fashion to general procedure 6, 2-{2-[(1 H-1 , 3-benzodiazol-2-ylmethyl)[(tert- butoxy)carbonyl]amino]ethyl}-1 , 3-thiazole-4-carboxylic acid (8) (150 mg, 0.373mmo), pyrimidin-4- ylmethanamine (48.8 mg , 0.447 mmol), DIPEA (48.1 mg, 0.373 mmol)and HATU (141.7 mg, 0.373 mmol) in DMF (2 ml) at room temperature overnight gave the title compound (80 mg, 60% purity) as an yellow oil after purification by flash column chromatography (eluting with a gradient of 10% MeOH in DCM). HPLCMS (Method H): [m/z]: 494.6 [M+H]+Step A: Benzyl 4-(pyrimidin-4-yl-methyl) piperazine-1-carboxylate (0110) To a stirred solution of 0.20 g (1.8 mmol) of

Molecular Weight:109.13
XLogP3:-1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:109.063997236
Monoisotopic Mass:109.063997236
Topological Polar Surface Area:51.8
Heavy Atom Count:8
Complexity:64.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes