Sodium Carbonate → HCID 178428242, compound

Participants

Reaction Conditions

Reaction Steps

Nitrogen was bubbled through a mixture of 2,6-Dichloro-4-(3-cyclopropyl-3-fluoroazetidine-1-yl)pyridine (1.0 g, 3.83 mmol), 5-methyl-1H-pyrazol-3-amine (0.7 g, 3.85 mmol), tris-(dibenzylideneacetone)dipalladium(0) (Pd2 dba3, 180 mg, 0.2 mmol), 9,9-dimethyl-4,5-bis(diphenyl-phosphino)xanthene (xantphos, 220 mg, 0.38 mmol), Na2CO3 (570 mg, 5.4 mmol), and 1,4-dioxane (12 mL) for about 15 minutes in a microwave vial. The vial was capped and heated in the microwave to 140° C. for 45 minutes and then to 170° C. for 15 minutes. The reaction mixture was filtered through Celite and rinsed with 1,4-dioxane. The solvent was removed under reduced pressure and the residue was dissolved in methanol/CH2Cl2 (1:1, 50 mL). Silica (2.5 g) was added and the solvents were removed under reduced pressure and the residue was brought on a column (100 mL silica in CH2Cl2/3% 2-propanol). The column was eluted with a gradient of 2-propanol (3-5%) in CH2Cl2. The fractions that contained the product (running with TLC RF=0.4 (SiO2, CH2Cl2/5% 2-propanol)) were pooled and concentrated to yield 450 mg (37%) of the title compound with 84/90% purity (HPLC, 215/254 nm). 1H-NMR (300 MHz, DMSO-d6): δ 11.74 (s, 1H); 9.02 (s, 1H); 6.38 (s, 1H); 5.88 (s, 1H); 5.84 (s, 1H); 3.94-3.78 (m, 4H); 2.15 (s, 3H); 1.42-1.03 (m, 1H); 0.62-0.57 (m, 2H); 0.44-0.40 (m, 2H) ppm.

Provenance & Evidence