Dimethylamine → 2-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Participants

Reaction Steps

To a solution of (2-chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol (6.24 g, 22.3 mmol) in DMF (100 mL) were added a solution of dimethylamine in THF (2 M, 46 mL, 4.1 equiv) and sodium cyanide (1.04 g, 0.95 equiv) and the resulting mixture was stirred at room temperature for 4 min. The reaction mixture was treated with manganese dioxide (100.4 g, 45 equiv) in four portions over 1 h and stirred for additional 1 h. The reaction mixture was filtered through a pad of Celite (rinsed with EtOAc 600 mL). The filtrate was washed with water (200 mL). The aqueous phase was extracted with EtOAc (2×150 mL). Combined organics were washed with 4% aqueous solution of NaCl (2×250 mL), dried over Na2SO4, filtered and concentrated in vacuo. Trituration of the residue in MeCN followed by column chromatography of the mother liquor (EtOAc/Heptane 30 to 100%) provided 2-chloro-7-cycloheptyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (6.07 g) in 85% yield. 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 6.52 (s, 1H), 4.63 (tt, J=11, 4.0 Hz, 1H), 3.20 (s, 3H), 3.11 (s, 3H), 2.52 (m, 2H), 1.99 (m, 2H), 1.88 (m, 2H), 1.70 (m, 4H), 1.58 (m, 2H) MS m/z 321.5 (M+H)+

Provenance & Evidence