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 931297노트

반응식

HRID 931297 반응식
C(O)(=O)C.[Cl:5][C:6]1[CH:7]=[N:8][N:9]([C:11]2([C:14](=[NH:18])OCC)[CH2:13][CH2:12]2)[CH:10]=1.[S].C(N(CC)CC)C.Cl.Cl.[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([N:37]2[CH2:42][CH2:41][CH2:40][C@@H:39]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:38]2)=[N:34][C:35]=1N>C(O)C>[Cl:5][C:6]1[CH:7]=[N:8][N:9]([C:11]2([C:14]3[NH:18][C:35]4=[N:34][C:33]([N:37]5[CH2:42][CH2:41][CH2:40][C@@H:39]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:38]5)=[CH:32][CH:31]=[C:30]4[N:29]=3)[CH2:12][CH2:13]2)[CH:10]=1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5362487SulfurHCID 117966385ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidateHCID 131735163(R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate dihydrochloride

생성물 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-carboxylate수율 48.9%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

Acetic acid (0.5 mL, 8.88 mmol), ethyl 1-(4-chloro-1H-pyrazol-1-yl)cyclopropanecarbimidate (445 mg, 1.78 mmol), a catalytic amount of sulfur, and triethylamine (0.8 mL, 5.92 mmol) were added to a suspension of (R)-ethyl 1-(5,6-diaminopyridin-2-yl)piperidine-3-carboxylate dihydrochloride (500 mg, 1.48 mmol) in ethanol (25 mL) at room temperature. The reaction mixture was heated at reflux for 18 h, then was concentrated under reduced pressure. The resulting residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via column chromatography (100-200 mesh 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 (300 mg). MS (ES+) (M+H) 415.2.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. concentrationwas concentrated under reduced pressure
  4. customThe resulting residue was partitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via column chromatography (100-200 mesh silica gel, 25-70% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-d9294e638bdd4f86a78a51079c255d58
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296745B2

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