4-(Trifluoromethyl)aniline → 6-Ethyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483228

反応式

HRID 1483228 の反応式
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.[C:12]([O-])(O)=[O:13].[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[NH2:29][C:30]1[S:40][C:33]2[CH2:34][N:35]([CH2:38][CH3:39])[CH2:36][CH2:37][C:32]=2[C:31]=1[C:41]([NH2:43])=[O:42]>C(Cl)Cl.C1COCC1>[CH2:38]([N:35]1[CH2:36][CH2:37][C:32]2[C:31]([C:41]([NH2:43])=[O:42])=[C:30]([NH:29][C:12](=[O:13])[NH:7][C:6]3[CH:8]=[CH:9][C:3]([C:2]([F:10])([F:11])[F:1])=[CH:4][CH:5]=3)[S:40][C:33]=2[CH2:34]1)[CH3:39]

参加物

7

反応物 4

HCID 99644-(Trifluoromethyl)anilineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 6144392-Amino-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

生成物 1

HCID 252384566-Ethyl-2-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide収率 31%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A vigorously stirred solution of 4-trifluoromethyl aniline (161 mg, 1.0 mmol) in DCM (3 mL) at room temperature was treated with aq. NaHCO3 (3 mL) and triphosgene (98 mg, 0.33 mmol) and the reaction mixture was vigorously stirred at room temperature for 45 min. 2-Amino-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide (225 mg, 1.0 mmol) was next added followed by THF and the reaction mixture was stirred at room temperature for 8 h. The solvent was then removed under vacuo and the resultant crude product was diluted with methanol and the insoluble solid was filtered off. Upon evaporation of MeOH, the crude oil was taken up in DCM and washed with water (×2), and the aqueous layer was back extracted with DCM. All organics were combined, dried (Na2SO4) and concentrated using a rotary evaporator. The crude product was purified by flash chromatography, Isolera system (SiO2 gel as stationary phase, 12 g HP column, dry loading) using DCM-DCM/MeOH (0%-10% MeOH in DCM) to afford the title compound as a brown solid (128 mg, 31% yield). MS (M+H) 413.

後処理

  1. additionnext added
  2. stirringthe reaction mixture was stirred at room temperature for 8 h
  3. customThe solvent was then removed under vacuo
  4. additionthe resultant crude product was diluted with methanol
  5. filtrationthe insoluble solid was filtered off
  6. customUpon evaporation of MeOH
  7. washwashed with water (×2)
  8. extractionthe aqueous layer was back extracted with DCM
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customa rotary evaporator
  12. customThe crude product was purified by flash chromatography, Isolera system (SiO2 gel as stationary phase, 12 g HP column, dry loading)

出典と根拠

ORDレコード
ord-8b471816f65e4b6996d5a00a3cf16823
出典データセット
uspto-grants-2016_08
特許番号
US09416141B2

関連ノート

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