Hydrochloric Acid → HCID 89544203, compound

Participants

Reaction Conditions

Reaction Steps

Example 1 (200 mg, 0.58 mmol) was partitioned between DCM (5 mL) and water (3 mL) basified to pH 12 with 5M NaOH. The organic phase was isolated by phase separator and blown down into a microwave vial. Acrylamide (41 mg, 0.58 mmol, 1 eq.) and MnCl2.4H2O (57 mg, 0.29 mmol, 0.5 eq.) was heated in ethanol (0.9 mL) and water (0.1 mL) in the microwave at 100 degC for 30 min. Only partial reaction, so further acrylamide and MnCl2 (same amounts) were added and the reaction heated for 30 min at 100° C. Still not complete so reaction heated as is for another 30 min at 100° C. The mixture then partitioned between EtOAc (15 mL) and water (10 mL) (plus drop of 5M NaOH) and then the aqueous extracted with further EtOAc (15 mL). Combined organics were washed with water (10 mL) and brine (10 mL) and then dried (MgSO+), filtered and concentrated. Purified by chiral HPLC normal phase, eluting EtOH and heptane. Concentrated and then dissolved in DCM (2 mL) and 1.1 eq. 2M HCl in Et2O added. Concentrated and dried in a vacuum oven to give 3-{[(1R)-1-{3-[(6-aminopyridin-3-yl)carbonyl]-4-chloro-2-fluorophenyl}propyl]amino}-propanamide (56 mg, 0.15 mmol, 25%) as an HCl salt and white solid.

Provenance & Evidence