2-Methyl-1H-imidazole-4-carboxylic acid

To a solution of 2-methyl-lH-imidazole-4-carbaldehyde (10 g, 91 mmol) in ACN (60 mL) at 0 °C, was added sulphamic acid (11 g, 120 mmol), and the reaction solution was stirred for 5 min before 2-methyl-2-butene (13 mL, 120 mmol) was added. A solution of sodium chlorite (11 g, 120 mmol) in water was added dropwise to mixture, and the solution was stirred for 4 hrs at rt. The MeCN was removed in vacuo, and the reaction mixture was quenched with 1.5N HC1 and extracted with EtOAc (250 mL x 3). The combined organics were washed with brine (200 mL), dried over Na[0688] the solution of compound 79a (500 mg, 3.96 mmol) in hcl/MeOH (4 m, 50 was stirred at 80 C for 12 hrs. The solvent was removed in vacuo. The residue was adjusted to ph ~ 8 with saturated aqueous NaHCO3. The solution was extracted with EtOAc (100 ml x 3). The organics were collected, dried with Na2SO4, filtered and concentrated. Compound 79b (360 mg, yield: 64.87%, light yellow solid): 1H NMR (CDCl3, 400 mhz) delta .90 - 7.88 (m, 1h), 7.34 - 7.31 (m, 1h), 7.15 - 7.09 (m, 2h), 5.72 - 5.63 (m, 1h), 4.87 - 4.76 (m, 2h), 2.90 - 2.86 (m, 2h), 1.92 - 1.87 (m, 2h), 1.50 - 1.47 (m, 2h), 1.26 - 1.14 (m, 8h).Compound 371.1. N, 2-Dimethyl-lH-imidazole-4-carboxamide. 2-Methyl-lH- imidazole-4-carboxylic acid (378 mg, 3 mmol), EDCI (745 mg, 3.9 mmol), HOBt (253 mg, 1.5 mmol), DIEA (1.6 mL, 9 mmol) and methyl amine (2M in THF) (3.6 mL, 7.2 mmol) were dissolved in DMF (10 mL) and stirred at room temperature for 16 hours. After removal of DMF, the residue was dry loaded and purified by flash chromatography (SiC^; 0-10 % methanol in DCM and 1% NH4OH) to give 280 mg (67%) of the title compound, m/z (ES+) 140 (M+H)+.a) (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-methyl-1H-imidazole-4-carboxamide 2-Methyl-1H-imidazole-4-carboxylic acid (29.0 g, 230 mmol), 335 ml of DMF and 165 ml of DCM were placed in to the reaction vessel under nitrogen. HBTU (7.27 g, 19.18 mmol), EDCI (44.1 g, 230 mmol) and 66.8 ml of DIPEA were added. (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (50 g, 192 mmol) was added and the reaction stirred overnight at RT. 600 ml of water was slowly added and water phase was washed with 335 ml and 500 ml of DCM. DCM phases were combined, washed with 3*600 ml of water and distilled to dryness. Acetonitrile (300 ml) was added and the mixture was heated up to 75 C. Water (300 ml) was added at >60 C., solution was allowed to cool to RT for precipitation and the mixture was stirred overnight at RT. Stirring was continued for additional 2 h at <10 C. The precipitate was filtered, washed with cold ACN:water and dried under vacuum to obtain 47 g of crude product. The title compound was recrystallized from EtOH with 75% yield. 1H-NMR (400 MHz, DMSO-d6): delta 1.08 (d, 3H), 2.30 (s, 3H), 4.23-4.48 (m, 3H), 6.95 (d, 1H), 7.41 (s, 1H), 7.82 (d, 1H), 7.95-8.07 (m, 3H), 8.09-8.12 (m, 1H), 12.12 (bs, 1H).

Molecular Weight:126.11
XLogP3:0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:126.042927438
Monoisotopic Mass:126.042927438
Topological Polar Surface Area:66
Heavy Atom Count:9
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes