N-methyl-2-pyrrolidone → HCID 59242734, compound

Participants

Reaction Conditions

Reaction Steps

Dissolve (S)-[4-(3-chloro-pyrazin-2-ylmethyl)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester (8.89 g, 21.7 mmol) in NMP (36 mL) and distribute the mixture evenly between three 10-20 mL microwave reactor vials. Cool each reaction vessel to 0° C. and sparge with anhydrous NH3 for 15 min. Seal each vessel and heat to 200° C. for 1 h in a microwave reactor. Combine the reaction mixtures together in water (500 mL) and sonicate for 20 min. Filter off a tan solid, then dissolve the solid in EtOAc (500 mL). Dry the organics (MgSO4), filter, and concentrate to a volume of 10 mL. Dilute the organics with MeOH (20 mL) and CH2Cl2 (10 mL) and absorb onto silica gel in vacuo. Purify on silica gel (340 g) using 1-10% (2 M NH3/MeOH)/(1:1 CH2Cl2/hexanes) to afford 1.50 g (18%) of the title compound as a yellow solid. MS (m/z) 391 (M+1), 389 (M−1). Pool and concentrate fractions containing impure product (1.2 g), and re-purify on silica gel (80 g) using 3-8% (2 M NH3/MeOH)/(1:1 CH2Cl2/hexanes) to afford a second crop (503 mg, 6%) of the title compound as a yellow solid.

Provenance & Evidence