Acetic Acid → (R)-ethyl 1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylate

Reaction equation

C(O)(=O)C.[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([N:13]2[CH2:18][CH2:17][CH2:16][C@@H:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:14]2)=[N:10][C:11]=1[NH2:12].Cl.[Cl:25][C:26]1[CH:27]=[N:28][N:29]([C:31]2([C:34](=N)OCC)[CH2:33][CH2:32]2)[CH:30]=1>>[Cl:25][C:26]1[CH:27]=[N:28][N:29]([C:31]2([C:34]3[NH:12][C:11]4=[N:10][C:9]([N:13]5[CH2:18][CH2:17][CH2:16][C@@H:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:14]5)=[CH:8][CH:7]=[C:6]4[N:5]=3)[CH2:33][CH2:32]2)[CH:30]=1

Participants

Reactant 3

HCID 176Acetic Acid

HCID 117966593ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate hydrochloride salt

HCID 131735159(R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate

Product 1

HCID 178472506(R)-ethyl 1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylate

Procedure

Acetic acid (2.5 mL, 41.66 mmol) was added to a solution of (R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate, prepared in step 2, followed by ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate hydrochloride salt, prepared in step 3). The mixture was heated at reflux for 18 h, then cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via column chromatography (100-200 silica gel, 25-70% ethyl acetate in petroleum ether) to afford (R)-ethyl 1-(2-(1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylate (900 mg). MS (ES+) (M+H) 415.2; LCMS retention time 2.506 min (Method N1).