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 931313ノート

反応式

HRID 931313 の反応式
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

参加物

6

反応物 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

生成物 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収率 81.2%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ce7a3ac5e0d74da7846d8ae87da8db76
出典データセット
uspto-grants-2016_03
特許番号
US09296745B2

反応ノート

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