1,2-Dichloroethane → HCID 67497658, compound

Participants

Reaction Conditions

Reaction Steps

To a 100 ml flask was added (2S)-2-amino-3-(4-fluorophenyl)-N-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)propanamide TFA (85 mg, 0.182 mmoles), 5 ml of DCE, DIEA (48 μl, 0.27 mmole, Make sure pH=7), 50 ul of AcOH and thiazole-4-carbaldehyde (16 mg, 0.15 mmole). The reaction was stirred at 65° C. for 5 minutes at which time sodium triacetoxyborohydride (116 mg, 0.55 mmoles) was added and stirred at 65° C. for an additional 30 minutes. The solvent was then removed and the crude purified by reverse phase preparative HPLC to give (2S)-2-amino-3-(4-fluorophenyl)-N-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)propanamide HCl (27.8 mg, 34% yield) after salt exchange using 1 M HCl in ether (546 ul, 0.55 mmole). LCMS ESI (pos.) m/e: 451.1 (M+1): 1H NMR (500 MHz, MeOH-d) δ ppm 9.04 (d, J=1.22 Hz, 1H) 8.50 (d, J=6.11 Hz, 1H) 8.16 (s, 1H) 8.11 (d, J=6.11 Hz, 1H) 7.78 (s, 1H) 7.25 (dd, J=8.19, 5.26 Hz, 2H) 6.95-7.10 (m, 3H) 4.44 (s, 2H) 4.41 (dd, J=8.93, 5.99 Hz, 1H) 3.56 (s, 3H) 3.40 (dd, J=13.33, 5.50 Hz, 1H) 3.15 (dd, J=13.57, 9.41 Hz, 1H) 2.70 (s, 3H).

Provenance & Evidence