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 931289Notes

Reaction equation

HRID 931289 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

4

Reactant 3

HCID 176Acetic AcidHCID 117966593ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate hydrochloride saltHCID 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).

Workup

  1. customprepared in step 2
  2. customprepared in step 3)
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 18 h
  5. temperaturecooled
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was partitioned between ethyl acetate and water
  8. dry with materialThe organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified via column chromatography (100-200 silica gel, 25-70% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-ff32c20ed3c14485b99de7fe3f391a52
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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