Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 66830568, compound

Participants

Reaction Steps

2,4-Dichloro-5-trifluoromethylpyrimidine (124 mg, 0.571 mmol), 2-methoxy-4-morpholin-4-yl-phenylamine (104 mg, 0.499 mmol), and N,N-diisopropylethylamine (97 mg, 0.75 mmol) were dissolved in 3 mL isopropyl alcohol and stirred at room temperature overnight. The reaction was concentrated and the organics dissolved in dichloromethane. The dichloromethane solution was washed with saturated sodium bicarbonate solution, was dried (sodium sulfate) and was concentrated. ISCO chromatography (0.75% MeOH:dichloromethane) afforded an inseparable mixture of both possible regioisomers (211 mg). This mixture (30 mg) was microwaved (130° C., 3 hours) with 3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (16 mg, 0.084 mmol) and 10-camphorsulfonic acid 22 mg, 0.095 mmol) in isopropyl alcohol (3 mL). On cooling, the mixture was concentrated and the organics were extracted in dichloromethane. The dichloromethane solution was washed with saturated sodium bicarbonate solution, was dried (sodium sulfate), and was concentrated. ISCO chromatography (gradient elution: 1 to 10% MeOH:dichloromethane) affords the title compound—a white solid (20 mg, 50%). Mp: 167-70° C. LCMS (m/e) 543 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.30 (s, 1H), 8.06 (d, J=9 Hz, 1H), 7.55 (br s, 2H), 7.36 (s, 1H), 7.22 (br s, 1H), 7.10 (d, J=9 Hz, 1H), 6.78 (s, 1H), 6.50 (s, 1H), 6.38 (br s, 1H), 3.90 (m, 7H), 3.15 (m, 4H), 3.00 (m, 4H), 2.80-2.60 (m, 6H), 1.20 (d, J=7 Hz, 3H).

Provenance & Evidence