N-methyl-2-pyrrolidone → HCID 178455822, compound

Participants

Reaction Conditions

Reaction Steps

A microwave reaction vial was charged with 5-chloro-4-((2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)(hydrazono)methyl)-1H-pyrrolo[2,3-b]pyridine (0.900 g, 2.11 mmol) and NMP (14.1 mL). Sodium tert-butoxide (0.506 g, 5.27 mmol), palladium(II) acetate (0.047 g, 0.211 mmol) and ((R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine (0.117 g, 0.211 mmol) were added sequentially and the mixture was heated in a microwave at about 150° C. for about 1 h (250 psi maximum pressure, 1 min ramp, 150 max watts). EtOAc (20 mL) was added and the mixture was filtered through a pad of Celite® while washing with EtOAc (20 mL). Water (15 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL), the combined organics were washed with water (3×10 mL), brine (5×10 mL), dried over anhydrous MgSO4, filtered and concd under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 40-100% EtOAc in heptane followed by purification using General Procedure AA to give 1-((1S,2S,4R)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine or 1-((1R,2R,4S)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine (0.065 g, 8%, Table 2, Method 35, Rt=20.0 min, or =positive) and 1-((1S,2S,4R)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine or 1-((1R,2R,4S)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine (0.058 g, 7%, Table 2, Method 35, Rt=23.4 min, or =negative): LC/MS (Table 1, Method b) Rt=2.26 min; MS m/z: 391 (M+H)+.

Provenance & Evidence