Dimethylformamide → methyl (2S)-6-(1-[1-[(tert-butoxy)carbonyl]-3-hydroxypiperidin-4-yl]-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

HRID 1051668노트

반응식

HRID 1051668 반응식
[CH:1]1([O:5][C:6]2[C:15]([C:16]3[CH:17]=[N:18][NH:19][CH:20]=3)=[CH:14][CH:13]=[C:12]3[C:7]=2[CH2:8][CH2:9][C@H:10]([CH3:25])[N:11]3[C:21]([O:23][CH3:24])=[O:22])[CH2:4][CH2:3][CH2:2]1.CN(C)C=O.[H-].[Na+].[CH:33]12[O:39][CH:38]1[CH2:37][CH2:36][N:35]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:34]2>C(OCC)(=O)C>[C:43]([O:42][C:40]([N:35]1[CH2:36][CH2:37][CH:38]([N:19]2[CH:20]=[C:16]([C:15]3[C:6]([O:5][CH:1]4[CH2:2][CH2:3][CH2:4]4)=[C:7]4[C:12](=[CH:13][CH:14]=3)[N:11]([C:21]([O:23][CH3:24])=[O:22])[C@@H:10]([CH3:25])[CH2:9][CH2:8]4)[CH:17]=[N:18]2)[CH:33]([OH:39])[CH2:34]1)=[O:41])([CH3:46])([CH3:44])[CH3:45]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 21991116tert-Butyl 7-Oxa-3-azabicyclo(4.1.0)heptane-3-carboxylateHCID 118075439(S)-methyl 5-cyclobutoxy-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1 (2H)-carboxylate

생성물 1

HCID 118086271methyl (2S)-6-(1-[1-[(tert-butoxy)carbonyl]-3-hydroxypiperidin-4-yl]-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate수율 78.4%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A 100-mL round-bottom flask was charged with (S)-methyl 5-cyclobutoxy-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (200 mg, 0.59 mmol) and N,N-dimethylformamide (10 mL). Sodium hydride (47 mg, 1.96 mmol) was added and the mixture stirred at room temperature for 30 minutes. tert-Butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (995 mg, 4.99 mmol) was added, and the resulting solution stirred overnight at 80° C. in an oil bath. After cooling to room temperature, the reaction mixture was poured into ethyl acetate (50 mL), washed with water (3×10 mL) and brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 10:1, dichloromethane/methanol) to afford methyl (2S)-6-(1-[1-[(tert-butoxy)carbonyl]-3-hydroxypiperidin-4-yl]-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate (250 mg, 78%) as yellow oil. MS (ESI, pos. ion) m/z 541 [M+H]+.

후처리

  1. stirringthe resulting solution stirred overnight at 80° C. in an oil bath
  2. temperatureAfter cooling to room temperature
  3. washwashed with water (3×10 mL) and brine (10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified via column chromatography on silica gel (eluting with 10:1, dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-c1292c020188495984d1dcc62f806ba0
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388161B2

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