Reaction Steps
Dissolve N-[9-(2-amino-benzyl)-6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 109) (193 mg, 0.5 mmol) in anhydrous DMF (2 mL) under nitrogen. Add acetaldhyde (0.34 mL, 0.6 mmol), sodium triacetoxyborohydride (191 mg, 0.9 mmol) and acetic acid (0.072 ml, 1.25 mmol) and heat at 40° C. for 6 h. Take TLC (1 hexane/3 ethyl acetate) and observe starting material is still present. Add more acetaldehyde (0.010 mL, 0.18 mmol), sodium triacetoxyborohydride (60 mg, 0.3 mmol) and acetic acid (0.030 mL, 0.5 mmol) and heat at 40° C. for 18 h. Observe TLC which shows the reaction still not complete 1 0 but new by-product is forming. Allow the reaction to cool, dilute with water (20 mL), and extract with ethyl acetate (3×20 mL). Combine the organic portions and wash with brine (40 mL), dry (MgSO4), filter, and concentrate in vacuo to give 416 mg of a brown solid. Absorb on silica with THF and a small amount of methanol and purify by flash chromatography. Elute with dichloromethane, then 10% ethyl acetate/dichloromethane with a gradient up to 50% ethyl acetate/dichloromethane to obtain 103 mg (50%) of a white solid. MS (ES): m/z 415 (M+1), 413 (M−1); 1H NMR(DMSO-d6): δ 8.02 (s, 1H), 7.88 (d, 1H, J=7.5 Hz), 7.41 (d, 2H, J=0.9 Hz), 7.07 (t, 1H, J=7.7 Hz), 6.67 (d, 1H, J=7.9 Hz), 6.42 (t, 1H, J=7.6 Hz), 5.85 (d, 1H, J=7.4 Hz), 5.25 (s, 2H), 5.06 (t, 1H, J=5.3 Hz), 4.04 (m, 1H), 3.17 (m, 2H), 3.04 (dd, 1H, J=15.4, 5.3 Hz), 2.74-2.55 (m, 3H), 2.41 (m, 1H), 1.97 (m, 1H), 1.83 (m, 1H), 1.28 (t, 3H, J=7.0 Hz), 1.02 (m, 6H).
