1-Propanol → HCID 89630011, compound

Participants

Reaction Steps

4-(2-Methyl-2H-indazol-6-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (50 mg, 0.12 mmol), HATU (90 mg, 0.24 mmol), and propanol (14.2 mg, 0.236 mmol) were added to DMSO (1.0 mL), followed by Hunig's base (0.103 mL, 0.590 mmol). The reaction was then stirred for 17 hours at room temperature at which point additional HATU (90 mg, 0.236 mmol), Hunig's base (0.103 mL, 0.590 mmol) and propanol (14.2 mg, 0.236 mmol) were added and the reaction stirred for an additional 17 hours at room temperature. Saturated aqueous sodium bicarbonate and EtOAc were added to the reaction mixture. The organic layer was separated and the aqueous layer extracted with EtOAc (×3). The combined organic layers were then washed with brine, dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in DMSO (1 mL) and CsF (179 mg, 1.18 mmol) was then added. The reaction mixture was heated at 140° C. for 2 hours open to the air. Upon cooling, the solution was made acidic by addition of TFA. The reaction mixture was then filtered and purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Pure fractions were combined and then saturated aqueous sodium bicarbonate was added. The organic layer was separated and the aqueous layer extracted with 3:1 CHCl3:IPA (×3). The combined organic layers were then washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford propyl 4-(2-methyl-2H-indazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate as a solid. LRMS (ESI) calc'd for C18H18N5O2 [M+11]+: 336; found 336. 1H NMR (600 MHz, DMSO-D6) δ 13.01 (s, 1H), 8.91 (s, 1H), 8.40 (s, 1H), 8.30 (s, 1H), 7.78 (s, 1H), 7.76 (d, 1H, J=8.80 Hz), 7.36 (d, 1H, J=8.80 Hz), 4.22 (s, 3H), 3.68 (t, 2H, J=6.45 Hz), 1.03 (m, 2H), 0.55 (t, 3H, J=7.04 Hz).

Provenance & Evidence