Potassium Carbonate → 5-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[4-(methylsulfonyl)phenyl]amino}thiophene-3-carboxamide

HRID 1967151

反応式

HRID 1967151 の反応式
[NH2:1][C:2]1[S:3][C:4]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17]([OH:20])([CH3:19])[CH3:18])=[CH:12][C:11]=2[F:21])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].[CH3:22][S:23]([C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1)(=[O:25])=[O:24].C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCO>[F:16][C:15]1[CH:14]=[C:13]([C:17]([OH:20])([CH3:18])[CH3:19])[CH:12]=[C:11]([F:21])[C:10]=1[C:4]1[S:3][C:2]([NH:1][C:29]2[CH:30]=[CH:31][C:26]([S:23]([CH3:22])(=[O:25])=[O:24])=[CH:27][CH:28]=2)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 770141-Bromo-4-(methylsulphonyl)benzeneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 595256192-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

生成物 1

HCID 446100635-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[4-(methylsulfonyl)phenyl]amino}thiophene-3-carboxamide

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 702Ethanol溶媒

反応条件

温度
100 °C

実験手順

2-amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (0.1 g, 0.320 mmol), 4-bromophenyl methyl sulfone (0.075 g, 0.320 mmol), Pd2 dba3 (0.029 g, 0.032 mmol), K2CO3 (0.049 g, 0.352 mmol) and X-Phos (0.076 g, 0.160 mmol) were added to a 5 mL microwave vial. Degassed EtOH (1 mL) was added and the vial evacuated and back-filled with N2 (×3). The resulting mixture was stirred at 100° C. overnight. Room temperature was attained, MeOH was added and the solvent removed in vacuo while loading onto silica. Purification of the residue by MPLC (0-10% MeOH—CHCl3) gave 5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[4-(methylsulfonyl)phenyl]amino}thiophene-3-carboxamide as a beige solid after triturating in DCM.

後処理

  1. customthe vial evacuated
  2. additionback-filled with N2 (×3)
  3. customRoom temperature
  4. additionMeOH was added
  5. customthe solvent removed in vacuo
  6. customPurification of the residue by MPLC (0-10% MeOH—CHCl3)

出典と根拠

ORDレコード
ord-3990bd39f71a43ddafd560707804bd84
出典データセット
uspto-grants-2013_04
特許番号
US08420695B2

関連ノート

読み込み中…