1,2-Dichloroethane → HCID 67497514, 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 diTFA (120 mg, 0.21 mmole), 3 ml of DCE, DIEA (90 μl, 0.52 mmole, make sure pH=7), 75 μl of AcOH and glyoxylic acid monohydrate (19 mg, 0.21 mmole). The reaction was stirred at 65° C. for 5 minutes at which time was added sodium triacetoxyborohydride (131 mg, 0.62 mmole) and stirred at 65° C. for an additional 18 hours. The solvent was then removed and the crude purified by reverse phase preparative HPLC to give 2-((S)-3-(4-fluorophenyl)-1-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid dihydrochloride 16.2 as a yellow solid (20.7 mg, 21 mmol, yield) after salt exchange using 4 M HCl in dioxane (155 μl, 0.62 mmole). LCMS ESI (pos.) m/e: 412.1 (M+1): 1H NMR (400 MHz, MeOH) δ ppm 8.61 (d, J=6.26 Hz, 1H), 8.21 (d, J=6.65 Hz, 1H), 8.26 (s, 1H), 7.39 (dd, J=8.41, 5.28 Hz, 2H), 7.07-7.20 (m, 3H), 4.52 (br. s., 1H), 3.94-4.06 (m, 2H), 3.67-3.70 (m, 3H), 3.46 (m, 1H), 3.29 (m, 1H), 2.80 (s, 3H).

Provenance & Evidence