Triethylamine → HCID 58379677, compound

Participants

Reaction Conditions

Reaction Steps

To a heterogeneous mixture of N-benzyl-2,2-dimethyl-N-prop-2-yn-1-ylpropanamide (222 mg, 0.968 mmol, from Step A), 5-bromo-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (218 mg, 0.692 mmol, described in Intermediate 5), CuI (7.0 mg, 0.35 mmol), tris(2-methylphenyl)phosphine (84.0 mg, 0.277 mmol) and triethylamine (0.6 mL), in DMF (0.8 mL), while under a nitrogen atmosphere, was added bis[tris(2-methylphenyl)phosphine]palladium (II) chloride (109 mg, 0.138 mmol). The reaction mixture was then heated to 50° C. for 20 hours. An additional amount of alkyne (2 drops), tris(2-methylphenyl)phosphine (40 mg) and palladium salt (50 mg) was added and the reaction was allowed to stir an additional 2 hours. The reaction was then diluted with water and EtOAc. The organics were separated and then washed with water (×5), then with brine (×1). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo to provide a residue. The residue was then applied to a silica gel column for partial purification, eluting with a gradient of 15-80% EtOAc in hexanes to give slightly impure title compound. This impure material was then applied to a silica gel column for purification, eluting with a gradient of 1-7% MeOH in DCM to give the title compound. MS: m/z=464 (M+1). Human CGRP receptor binding Ki=20 nM. HRMS: m/z=464.2346; calculated m/z=464.2333 for C30H30N3O2.

Provenance & Evidence