Oxalyl chloride → HCID 131735780、化合物

HRID 2202768ノート

反応式

HRID 2202768 の反応式
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][C:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([N:18]2[C:22]([C:23]([F:26])([F:25])[F:24])=[C:21]([C:27](O)=[O:28])[CH:20]=[N:19]2)[CH2:14][C@H:13]1[CH3:30])=[O:11])[CH3:8].[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[N:34][CH:35]=[C:36]([Cl:46])[C:37]=1[CH2:38][CH2:39][NH:40][CH2:41][C:42]([CH3:45])([CH3:44])[CH3:43].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[N:34][CH:35]=[C:36]([Cl:46])[C:37]=1[CH2:38][CH2:39][N:40]([CH2:41][C:42]([CH3:45])([CH3:43])[CH3:44])[C:27]([C:21]1[CH:20]=[N:19][N:18]([C@H:15]2[CH2:16][CH2:17][C@H:12]([C:10]([O:9][CH2:7][CH3:8])=[O:11])[C@H:13]([CH3:30])[CH2:14]2)[C:22]=1[C:23]([F:24])([F:26])[F:25])=[O:28]

参加物

7

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 118343005HCID 118343005、化合物HCID 118349845HCID 118349845、化合物

生成物 1

HCID 131735780HCID 131735780、化合物収率 82%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

実験手順

Oxalyl chloride (2.0M in DCM, 0.52 mL, 1.03 mmol) was added to a solution of 1-((1S,3R,4S)-4-(ethoxycarbonyl)-3-methylcyclohexyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (239 mg, 0.687 mmol) in DCM (2.0 mL) followed by 1 drop of DMF while cooling in an ice bath. The solution was removed from the ice bath and allowed to stir at room temperature for 1 h. The reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator) and the crude residue was treated with DCM (2.0 mL) and cooled to 0° C. The stirring solution was then treated with N-(2-(3,5-dichloro-2-methoxypyridin-4-yl)ethyl)-2,2-dimethylpropan-1-amine (200 mg, 0.687 mmol) in DCM (2 mL) followed by the addition of DIPEA (0.36 mL, 2.06 mmol) and allowed to warm to room temperature and stirred overnight (16 h). The reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator) and the crude residue was purified on an ISCO Combiflash™ RF (25 g Grace Reveleris column, using a gradient of 0-50% EtOAc in heptane) affording (1S,2R,4S)-ethyl 4-(4-((2-(3,5-dichloro-2-methoxypyridin-4-yl)ethyl)(neopentyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2-methylcyclohexanecarboxylate (350 mg, 0.56 mmol, 82% yield) as a white crystalline solid. MS (ESI) 621.2, 623.2 [M+H]+.

後処理

  1. temperaturewhile cooling in an ice bath
  2. customThe solution was removed from the ice bath
  3. concentrationThe reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator)
  4. additionthe crude residue was treated with DCM (2.0 mL)
  5. temperaturecooled to 0° C
  6. temperatureto warm to room temperature
  7. stirringstirred overnight (16 h)
  8. concentrationThe reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator)
  9. customthe crude residue was purified on an ISCO Combiflash™ RF (25 g Grace Reveleris column

出典と根拠

ORDレコード
ord-83bf61266e8a4c5fb2e53b008d3d663c
出典データセット
uspto-grants-2016_06
特許番号
US09365522B2

反応ノート

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