Triethylamine → HCID 178434460, compound

Participants

Reaction Conditions

Reaction Steps

Charge a 100 mL round-bottomed flask with 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (0.103 g, 0.442 mmol obtained from Example 19, step C), and CH2Cl2 (10 mL). Oxalyl chloride in DCM (2M) (2.84 ml, 5.68 mmol) and DMF (3 drops) were added. The reaction mixture was stirred for 1 hour and concentrated. The crude material was resuspend in DCM and 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2,5-difluorobenzenamine (0.750 g, 1.89 mmol), N,N-dimethylpyridin-4-amine (0.0231 g, 0.189 mmol) and triethylamine (0.287 g, 2.84 mmol) were added. The reaction mixture was stirred at r ambient temperature for 16 hours, then diluted with water and DCM. The organic layer washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by chromatography, eluting with EtOAc and concentrated. To the crude material in a 25 mL RBF was add TFA (3 mL). The mixture was heated to 70° C. for 2 hours, then cooled to ambient temperature and concentrated. The residue was triturated with DCM/MeOH 1:1 (5 mL) to afford 461 mg (46%) of the desired product. LRMS M+1 (493.1) observed. 1H NMR (400 MHz, DMSOd6) δ12.14 (s, 1H), 8.54 (s, 1H), 8.43 (m, 1H), 8.36 (m, 1H), 8.30 (m, 1H), 7.77 (m, 1H), 7.68 (m, 2H), 7.42 (t, J=8 Hz, 2H), 6.35 (d, J=5 Hz, 1H), 2.62 (s, 3H).

Provenance & Evidence