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

HRID 931313Notes

Reaction equation

HRID 931313 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:24][C:25]1[CH:26]=[N:27][N:28]([C:30]2([C:33](=N)OCC)[CH2:32][CH2:31]2)[CH:29]=1.C(N(CC)CC)C>C(O)C>[Cl:24][C:25]1[CH:26]=[N:27][N:28]([C:30]2([C:33]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)[CH2:32][CH2:31]2)[CH:29]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 117966385ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidateHCID 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-carboxylateYield 81.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Acetic acid (4.3 g, 67.2 mmol) was added to a solution of (R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate (890 mg, 3.36 mmol), ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate (445 mg, 1.78 mmol) and triethylamine (0.8 mL, 5.92 mmol) in ethanol (25 mL) at room temperature under a nitrogen atmosphere. The mixture was heated at reflux for 16 h, then was concentrated under reduced pressure. The resulting residue was partitioned between ethyl acetate and water. The organics were dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified via column chromatography (100-200 mesh silica gel, 20-60% 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 (600 mg). MS (ES+) (M+H) 415.2859.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. concentrationwas concentrated under reduced pressure
  4. customThe resulting residue was partitioned between ethyl acetate and water
  5. dry with materialThe organics were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified via column chromatography (100-200 mesh silica gel, 20-60% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-ce7a3ac5e0d74da7846d8ae87da8db76
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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