Diisopropylethylamine → HCID 67538875, compound

Participants

Reaction Steps

PyBrop (407 mg, 0.87 mmol) was added in a single portion to a solution of (R)—N-Boc-4-chlorophenylalanine (458 mg, 1.53 mmol) and 4-piperazin-1-yl-1H-pyrrolo[2,3-b]pyridine (200 mg, 0.73 mmol) in DCM (5 mL) cooled in an ice bath. DIEA (0.66 mL, 3.78 mmol) was then dropped in, the ice bath was removed, and the mixture was stirred for 12 hours at ambient temperature. The mixture was diluted with DCM and washed with 0.1N HCl. The separated DCM layer was dried (Na2SO4), filtered, and concentrated in vacuo. This material was dissolved in MeOH (4 mL) followed by the addition of LiOH monohydrate (122 mg, 2.91 mmol) in H2O (2 mL) and stirred for 12 hours. The mixture was concentrated in vacuo and chromatographed (SiO2) using 2% MeOH/DCM followed by 5% MeOH/DCM as eluent. The resulting material was dissolved in DCM (4 mL) and 2.0 M HCl in Et2O (2 mL), and then stirred for 12 hours. The mixture was concentrated in vacuo and chromatographed (SiO2) using 10% MeOH/DCM followed by 10% (7N NH3 in MeOH)/DCM as eluent. The purified material was dissolved in MeOH followed by the addition of 2.0N HCl in Et2O, and then concentrated in vacuo. The resulting glass was suspended in Et2O and concentrated in vacuo (repeat twice) to give 2-(R)-amino-3-(4-chlorophenyl)-1-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride as an off-white powder (50 mg). 1H NMR (DMSO-d6, 400 MHz) δ 12.6 (s, 1H), 8.56 (bs, 3H), 8.03 (d, J=7.1 Hz, 1H), 7.38 (m, 3H), 7.32 (m, 2H), 6.84 (s, 1H), 6.69 (d, J=7.1 Hz, 1H), 4.63 (bs, 1H), 3.88-3.58 (m, 7H), 3.33 (m, 1H), 3.14 (m, 1H), 3.05 (m, 1H). LCMS (APCI+) m/z 384, 386 [M+H]+.

Provenance & Evidence