Pyridine → HCID 59161244, compound

Participants

Reaction Steps

Suspend N-[9-(2-amino-benzyl)-6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 109) (116 mg, 0.3 mmol) in anhydrous dichloromethane (3 mL) under nitrogen. Add methanesulfonyl chloride (0.028 mL, 0.36 mmol) and pyridine (0.032 mL, 0.39 mmol), followed by anhydrous DMF (2 mL) to effect solution. Stir 5.5 h at room temperature. Add additional methanesulfonyl chloride (0.010 mL, 0.13 mmol) and pyridine (0.010 mL, 0.12 mmol) and stir 18 h at room temperature. Dilute with dichloromethane and wash with 1N hydrochloric acid. Backwash the aqueous portion with dichloromethane. Combine the organic portions and wash with brine, dry (MgSO4), filter, and concentrate in vacuo to provide 74 mg of a yellow oil. Absorb the oil on silica with THF and a small amount of methanol and purify by flash chromatography. Elute with a step gradient of 10% ethyl acetate/dichloromethane, 25% ethyl acetate/dichloromethane, and 50% ethyl acetate/dichloromethane to obtain 19 mg (14%) of a light yellow solid. MS (ES): m/z 465 (M+1), 463 (M−1); 1H NMR(DMSO-d6): δ 9.43 (s, 1H), 8.02 (s, 1H), 7.88 (d, 1H, J=7.5 Hz), 7.43-7.36 (m, 3H), 7.31 (dt, 1H, J=7.6, 1.0 Hz), 7.12 (dt, 1H, J=7.5, 0.9 Hz), 6.21 (d, 1H, J=7.5 Hz), 5.54 (s, 2H), 4.06 (m, 1H), 3.12 (s, 3H), 3.04 (dd, 1H, J=15.4, 5.3 Hz), 2.70 (m, 2H), 2.59 (dd, 1H, J=15.4, 8.4 Hz), 2.41 (m, 1H), 1.97 (m, 1H), 1.85 (m, 1H), 1.02 (m, 6H).

Provenance & Evidence