Trifluoroacetic acid → HCID 86719390, compound

Participants

Reaction Steps

To a solution of (R)-tert-butyl 3-(4-amino-6-chloro-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (37) (made according to procedures described in examples 1 and 2, using 4-chlorophenylboronic acid) (70 mg, 0.16 mmol) in DCM (4.0 mL) was added TFA (1 mL). The resulting mixture was stirred at r.t. for 1 hr before concentrated down to dryness under reduced pressure. The residue was dissolved in DMF (3 mL) and DIPEA (0.08 mL, 0.49 mmol), (E)-4-(cyclopropyl(methyl)amino)but-2-enoic acid (100 mg, 0.31 mmol), HBTU (60.4 mg, 0.16 mmol) were added, respectively. The resulting mixture was stirred at r.t. for 30 min. The solvents were evaporated. The crude product was directly purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3H2O)) to afford (R,E)-1-(3-(4-amino-6-chloro-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)-4-(cyclopropyl(methyl)amino)but-2-en-1-one (38) (6.0 mg, 7.9% yield) as a white solid. LC-MS (ESI): m/z (M/M+2) 486.4/488.4. 1H NMR (400 MHz, DMSO) δ 8.17-8.12 (m, 1H), 7.56 (dd, J=8.4, 1.6 Hz, 2H), 7.48-7.40 (m, 2H), 6.77-6.60 (m, 1H), 6.37 (m, 1H), 6.10 (br, 1H), 5.49-5.28 (m, 1H), 4.24 (t, J=9.1 Hz, 1H), 4.17-3.93 (m, 1H), 3.91-3.75 (m, 1H), 3.69-3.53 (m, 1H), 3.05-2.59 (m, 3H), 2.38-2.27 (m, 1H), 2.20 (d, J=16.0 Hz, 3H), 1.82-1.46 (m, 1H), 0.48-0.36 (m, 2H), 0.32-0.18 (m, 2H).

Provenance & Evidence