1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxy-2-pyrazinecarboxamide

HRID 930281노트

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HRID 930281 반응식
C([NH:9][C:10]1[O:11][C@H:12]([C:36]([F:39])([F:38])[F:37])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[N:32][C:31]([O:34][CH3:35])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])([CH2:16][F:17])[N:15]=1)(=O)C1C=CC=CC=1.N12CCCN=C1CCCCC2>CO>[NH2:9][C:10]1[O:11][C@H:12]([C:36]([F:37])([F:39])[F:38])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[N:32][C:31]([O:34][CH3:35])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])([CH2:16][F:17])[N:15]=1

참가 물질

4

반응물 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86732110N-(3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide

생성물 1

HCID 71668202N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxy-2-pyrazinecarboxamide수율 83%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
75 °C

실험 절차

A microwave vial was charged with N-(3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide (0.11 g, 0.200 mmol, step 1). MeOH (2 ml) was added followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.122 g, 0.801 mmol, Aldrich). The vial was sealed and heated to 75° C. in a microwave (Biotage Initiator) for 1.5 hours. The reaction was cooled to RT and concentrated under reduced pressure. The crude material was purified via silica gel flash chromatography using a gradient of 5-70% EtOAc in hexanes to afford the title compound as a white solid (0.0741 g, 0.166 mmol, 83% yield). MS m/z=446.0 [M+H]+. Calculated for C18H16F5N5O3: 445.343

후처리

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled to RT
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified via silica gel flash chromatography

출처 및 근거

ORD 기록
ord-681bbc7f3a9f41c79610cbce4a9b5bf4
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296734B2

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