Acetyl chloride → 4-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide

Participants

Reaction Conditions

Reaction Steps

4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide resin (50 mg, 0.05 mmol), prepared as in reference 3, in n-butanol (2 mL) is mixed with acetyl chloride (17.8 μL, 0.25 mmol) and 3-(1-hydroxyethyl)aniline (34 mg, 0.25 mmol) and shaken at 80° C. for 24 hours. The resulting mixture is filtered and the resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes before filtering and washing with CH2Cl2 (3×2 mL), MeOH (3×2 mL). The washes are then combined together with n-butanol and concentrated. The residue is purified by preparative HPLC-MS to give 4-[3-(1-hydroxy-ethyl)-phenylamino]-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide (16.6 mg, yield 51%); 1HNMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.68 (s, 1H), 9.85 (s, 1H), 9.62 (s, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.54 (s, 1H), 8.47 (s, 1H), 8.43 (s, 1H), 8.17 (s, 1H), 7.85 (d, J=4.1 Hz, 2H), 7.70 (s, 1H), 7.61 (dd, J=6.5, 8.2 Hz, 1H), 7.35 (d, J=2.3 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 7.09 (s, 1H), 7.08 (d, J=6.8 Hz, 1H), 4.75 (q, J=6.4 Hz, 1H), 2.47 (s, 3H), 2.36 (s, 3H), 1.36 (d, J=6.4 Hz, 3H); ESIMS m/z 655.2 (M++1).

Provenance & Evidence