Formaldehyde → 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-2-methyl-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Participants

Reaction Steps

To a solution of 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (from example 89, enantiomer-2) (66 mg, 0.128 mmol, 1 eq) in THF (2.0 mL) was added 37% aquous solution of formaldehyde (0.048 mL, 0.639 mmol, 5 eq). The reaction mixture was stirred at room temperature for 5 minutes. Solid sodium triacetoxyhydroborate (81 mg, 0.383 mmol, 3 eq was added into the mixture. The reaction was stirred for 10 more minutes and quenched with a drop of TEA and naturalized with amonia in methanol. The residue was concentrated under vacuum and purified by column chromatography (NH3/MeOH/CH2Cl2) to provide 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7a R)-2-methyl-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (67 mg) in quantitative yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1H), 8.63 (d, J=9.09 Hz, 1H), 8.27 (s, 1H), 8.24 (d, J=2.53 Hz, 1H), 7.67 (dd, J1=9.09, J2=2.53 Hz, 1H), 6.44 (s, 1H), 4.73 (s, 3H), 4.52 (m, 1H), 3.83 (dd, J1=13.14, J2=4.04 Hz, 1H), 3.65 (dd, J1=13.14, J2=4.04 Hz, 1H), 3.17 (s, 6H), 2.91-2.51 (m, 7H), 2.36 (m, 4H), 2.01 (m, 2H), 1.87 (m, 2H), 1.79-1.51 (m, 5H); HRMS m/z 531.3219 (M+H)+.

Provenance & Evidence