4-fluoro-1-isocyanato-2-methylbenzene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluoro-1-isocyanato-2-methylbenzene (10 mg, 0.068 mmol) was added to a solution of 4-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (20 mg, 0.034 mmol; from Example 12, Step 2) and triethylamine (28 uL, 0.20 mmol) in THF (0.39 mL). The reaction was stirred for one hour, then solvent was removed in vacuo. The residue was stirred in a 1:1 mixture of DCM:TFA for 1 hour, concentrated, and stirred in a solution of methanol (1 mL) containing ethylenediamine (0.2 mL) for one hour. Purification via preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (11 mg, 67%). 1H NMR (400 MHz, d6-dmso): δ 12.12 (br s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.38 (s, 1H), 8.01 (s, 1H), 7.61 (d, 1H), 7.11 (dd, 1H), 7.02 (dd, 1H), 6.98 (d, 1H), 6.92 (dt, 1H), 5.01 (tt, 1H), 3.42-3.29 (m, 4H), 3.26-3.19 (m, 2H), 2.86 (dd, 1H), 2.81 (dd, 1H), 2.54-2.46 (m, 2H), 2.43-2.34 (m, 2H), 2.11 (s, 3H); LCMS (M+H)+: 488.3. solvent was removed in vacuo The residue was stirred in a 1:1 mixture of DCM TFA for 1 hour concentrated stirred in a solution of methanol (1 mL) containing ethylenediamine (0.2 mL) for one hour Purification via preparative HPLC-MS eluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (11 mg, 67%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 20% Phosgene in toluene (0.25 mL, 0.48 mmol) and triethylamine (0.11 mL, 0.76 mmol) were added to a solution of 4-fluoro-2-methyl-benzenamine (12 mg, 0.095 mmol) in a mixture of THF (0.30 mL) and DCM (0.10 mL). The reaction was stirred for two hours, then solvents were removed in vacuo and the product used without further purification in the next step. solvents were removed in vacuo the product used without further purification in the next step