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

HRID 930329
ノート
印刷プレビュー

反応式

HRID 930329 の反応式
C([NH:9][C:10]1[O:11][C@H:12]([C:35]([F:38])([F:37])[F:36])[CH2:13][C@:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([N:27]3[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]3)=[O:26])[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1)(=O)C1C=CC=CC=1.N12CCCN=C1CCCCC2>CO>[NH2:9][C:10]1[O:11][C@H:12]([C:35]([F:36])([F:38])[F:37])[CH2:13][C@:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([N:27]3[CH2:28][CH2:29][CH:30]([O:33][CH3:34])[CH2:31][CH2:32]3)=[O:26])[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86732157N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide

生成物 1

HCID 86732158N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide収率 51%

試薬・触媒・溶媒 1

HCID 887Methanol
溶媒
2 回

反応条件

温度
60 °C

実験手順

To a solution of N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide (0.166 g, 0.309 mmol) in MeOH (3 mL) at room temperature was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (0.100 mL, 0.669 mmol). The reaction was heated at 60° C. for 4 h. Then the reaction was cooled to room temperature, diluted with MeOH, purified by reverse-phase HPLC (Gilson; Gemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA CH3CN (9:1→1:9). The fractions containing the desired product were combined and concentrated in vacuo. The material was dissolved in MeOH and eluted with MeOH, through an Silicycle carbonate cartridge to give the titled compound as a white crystalline solid (68 mg, 51%). MS m/z=433 [M+H]+. Calculated for C19H24F4N4O3: 432

後処理

  1. temperatureThen the reaction was cooled to room temperature
  2. custompurified by reverse-phase HPLC (Gilson
  3. washGemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O
  4. additionThe fractions containing the desired product
  5. concentrationconcentrated in vacuo
  6. dissolutionThe material was dissolved in MeOH
  7. washeluted with MeOH, through an Silicycle carbonate cartridge

出典と根拠

ORDレコード
ord-da3b2fa1ef8b4e448ba0f07293efdf10
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09296734B2

反応ノート

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