1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(6-((4R,6S)-2-amino-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

HRID 930362ノート

反応式

HRID 930362 の反応式
C([NH:9][C:10]1[O:11][C@H:12]([C:36]([F:39])([F:38])[F:37])[CH2:13][C@@:14]([C:19]2[N:24]=[C:23]([NH:25][C:26](=[O:34])[C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=3)[CH:22]=[CH:21][C:20]=2[F:35])([CH:16]([F:18])[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:19]2[N:24]=[C:23]([NH:25][C:26](=[O:34])[C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=3)[CH:22]=[CH:21][C:20]=2[F:35])([CH:16]([F:17])[F:18])[N:15]=1

参加物

4

反応物 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86732182N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

生成物 1

HCID 86732183N-(6-((4R,6S)-2-amino-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide収率 13.8%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
80 °C

実験手順

To a solution of N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide (16 mg, 0.028 mmol) in MeOH (74.60 in a flask was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (336 μl, 2.249 mmol). The vial was sealed and was heated at 80° C. for 4 h. The reaction was diluted with MeOH and purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 70% over 16 min, then neutralized with solid NaHCO3 and extracted with DCM to provide N-(6-((4R,6S)-2-amino-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide (1.8 mg, 3.85 μmol, 13.75% yield) as a off-white solid. MS m/z=467, 469 M+; Calculated for C17H12ClF6N5O2: 467.75.

後処理

  1. customThe vial was sealed
  2. custompurified by reverse-phase preparative HPLC
  3. customover 16 min
  4. extractionextracted with DCM

出典と根拠

ORDレコード
ord-3a6d43d3ab524cf492e7010295fa35c4
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

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