Acetic Acid → HCID 178420339, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (5-Chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)((3R)-3-(dibenzylamino)cyclopentyl)methanone (1.5 g, 2.5 mmol), hydrazine (0.24 mL, 7.5 mmol), and AcOH (0.14 mL, 2.5 mmol) in EtOH (40 mL) was heated to reflux for about 8 h and at about 90° C. for about 16 h. The solvent was removed in vacuo and the residue was partitioned between saturated aqueous NaHCO3 (50 mL) and EtOAc (50 mL). The organic phase was separated and washed with brine (40 mL), dried over anhydrous MgSO4, filtered, and concentrated to yield crude (3R)-(3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentanamine (1.14 g, 100%) as a yellow amorphous solid that was used without purification. To a solution of the hydrazone (1.14 g, 2.5 mmol) in NMP (4 mL) were added sodium tert-butoxide (0.58 g, 6.0 mmol), palladium (II) acetate (0.0056 g, 0.025 mmol), and CyPFt-Bu (0.014 g, 0.025 mmol). The mixture was heated at about 140° C. for about 15 min in a microwave, and the solvent was removed under reduced pressure. The residue was partitioned between EtOAc (25 mL) and water (25 mL), and the organic solution was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to give crude (3R)—N,N-dibenzyl-3-(3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentanamine (1.05 g, 100%) as a dark brown solid that was used without purification. To a solution of the protected amine (1.05 g, 2.5 mmol) in MeOH (15 mL) was added Pd(OH)2 (0.23 g, 1.6 mmol) and ammonium formate (1.58 g, 25.0 mmol). The mixture was heated at about 65° C. for about 1 h. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to give crude (3R)-(3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentanamine (0.60 g, 100%) as a brown solid that was used without purification: LC/MS (Table 2, Method a) R=1.12 min; MS m/z: 242 (M+H)+.

Provenance & Evidence