Ethyl isonicotinate → Isonicotinamide, N-cyclopropyl-
Reaction equation
C(O[C:4](=[O:11])[C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1)C.[CH:12]1([NH2:15])[CH2:14][CH2:13]1>>[CH:12]1([NH:15][C:4](=[O:11])[C:5]2[CH:6]=[CH:7][N:8]=[CH:9][CH:10]=2)[CH2:14][CH2:13]1Participants
Procedure
Isonicotinic acid ethyl ester (3.0 g, 20 mmol) was mixed with cyclopropylamine (2 ml) at 120° C. in a sealed vial for 40 h. The reaction mixture was triturated with ether to give 1.62 g (50%) of N-cyclopropyl-isonicotinamide as off-white solid. 1H-NMR(CDCl3) d (ppm): 8.73 (d, 2H), 7.60 (d, 2H) and 6.55 (w, 1H), 2.92 (m, 1H), 0.90 (m, 2H) and 0.66 (m, 2H). Step 2: N-Cyclopropyl-isonicotinimidoyl chloride hydrochloride: N-Cyclopropyl-isonicotinamide (1.62 g, 10 mmol) was reacted with SOCl2 (12 g, 100 mol) at 80° C. overnight. The reaction mixture was concentrated and triturated with dichloromethane to give 1.3 g (64%) of N-cyclopropyl-isonicotinimidoyl chloride hydrochloride as yellow solid. Step 3: 4-(5-{2-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridine: (R)-3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid hydrazide (56 mg, 0.2 mmol) was mixed with N-cyclopropyl-isonicotinimidoyl chloride hydrochloride (40.6 mg, 0.2 mmol) and K2CO3 (60 mg, 0.43 mmol) in DMF (1 ml) at 100° C. for 3 h. The reaction mixture was dilute with dichloromethane and then washed with water. The organic layer was concentrated and purified with 5˜6% methanol in ethyl acetate to give 32 mg (39%) of the title comound. 1H-NMR(CDCl3) d (ppm): 8.78 (d, 2H), 8.05 (s, 1H), 7.96(d, 1H), 7.73(d, 2H), 7.45(m, 2H), 4.15 (q, 1H), 3.64 (dd, 1H), 3.31 (m, 2H), 1.68 (d, 3H), 1.25 (m, 2H) and 0.79 (m, 2H).
Workup
- customThe reaction mixture was triturated with ether
Sources & evidence
- ORD record
- ord-011aab0de4ab4850bc7558faaa5faf2d
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07585881B2
Reaction notes
Loading…