Methanesulfonyl chloride → HCID 86707710, compound

Participants

Reaction Steps

4-(N,N-dimethylamino)pyridine (15.7 mg, 0.129 mmol) was added to a solution of 4-((1R,3S)-3-amino-2,2,3-trimethylcyclopentylamino)-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (97.5 mg, 0.138 mmol, from Example 232), N,N-diisopropylethylamine (0.080 mL, 0.458 mmol) and methanesulfonyl chloride (0.030 mL, 0.385 mmol) in dichloromethane (1 mL). After 1 h at room temperature, the mixture was purified by silica gel chromatography, eluting with 0-10% methanol in dichloromethane. The fractions containing the desired product were concentrated. The material was further purified with reverse phase HPLC (Waters Xbridge 19×100 mm), eluting with 20-80% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), to give 6-(6-methoxy-3-pyridinyl)-4-(((1R,3S)-2,2,3-trimethyl-3-((methylsulfonyl)amino)-cyclopentyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide as white solid (25.1 mg, 37% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 8.47 (1 H, d, J=1.98 Hz), 8.15 (1 H, s), 8.07 (1 H, dd, J=8.58, 2.42 Hz), 7.95 (1 H, d, J=1.76 Hz), 7.15 (1 H, d, J=1.54 Hz), 6.94 (1 H, d, J=8.58 Hz), 4.58 (1 H, t, J=8.25 Hz), 3.98 (3 H, s), 3.06 (3 H, s), 2.42-2.53 (2 H, m), 1.93-2.05 (1 H, m), 1.73-1.84 (1 H, m), 1.53 (3 H, s), 1.16 (3 H, s), 1.04 (3 H, s); MS (ES+) m/z: 487.3 (M+H); LC retention time: 3.843 min (analytical HPLC Method F).

Provenance & Evidence