2-(Trifluoromethyl)aniline → 6-(3-Ethylureido)-4-(phenylamino)-N-(2-(trifluoromethyl)phenyl)nicotinamide

HRID 2174239ノート

反応式

HRID 2174239 の反応式
CS(Cl)(=O)=O.[CH2:6]([NH:8][C:9](=[O:27])[NH:10][C:11]1[CH:19]=[C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:14]([C:15]([OH:17])=O)=[CH:13][N:12]=1)[CH3:7].N1C(C)=CC=CC=1C.[F:36][C:37]([F:46])([F:45])[C:38]1[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=1[NH2:40]>CC(N(C)C)=O>[CH2:6]([NH:8][C:9](=[O:27])[NH:10][C:11]1[CH:19]=[C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:14]([C:15]([NH:40][C:39]2[CH:41]=[CH:42][CH:43]=[CH:44][C:38]=2[C:37]([F:36])([F:45])[F:46])=[O:17])=[CH:13][N:12]=1)[CH3:7]

参加物

6

反応物 4

HCID 69222-(Trifluoromethyl)anilineHCID 79372,6-LutidineHCID 31297Methanesulfonyl chlorideHCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acid

生成物 1

HCID 716208506-(3-Ethylureido)-4-(phenylamino)-N-(2-(trifluoromethyl)phenyl)nicotinamide収率 8%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒3 回

反応条件

温度
0 °C

実験手順

An ice-cold solution of methane sulfonyl chloride (18 μL, 0.23 mmol) in DMA (2.0 mL) was stirred for 10 min followed by sequential drop wise addition of a solution of 6-(3-ethylureido)-4-(phenylamino)nicotinic acid (50 mg, 0.16 mmol) in DMA (5.0 mL) and 2,6-lutidine (55 μL, 0.46 mmol). The resulting reaction mixture was stirred at 0° C. for 30 min followed by addition of a solution of 2-trifluoromethyl aniline (31 μL, 0.25 mmol) in DMA (1.0 mL). The reaction mass was further stirred at RT ° C. for 10 min and then heated at 50° C. for 4 h. The reaction mass was then cooled to 0-5° C. and quenched with H2O (5.0 mL), followed by addition of conc. HCl (0.50 mL). The resulting solution was stirred for 5 min followed by extraction with EtOAc (3×50 mL). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified via preparative TLC to obtain Compound 11 (5.0 mg, 8%). 1H NMR (300 MHz, DMSO-d6): δ 10.23 (br s, 1H), 10.07 (br s, 1H), 9.12 (br s, 1H), 8.61 (s, 1H), 7.89 (m, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.74 (m, 1H), 7.57 (m, 2H), 7.38-7.43 (m, 2H), 7.31 (s, 1H), 7.25 (m, 2H), 7.15 (m, 1H), 3.14 (m, 2H) and 1.06 (t, J=7.20 Hz, 3H). [M+H]+ m/z=444.17.

後処理

  1. customThe resulting reaction mixture
  2. stirringThe reaction mass was further stirred at RT ° C
  3. waitfor 10 min
  4. temperatureheated at 50° C. for 4 h
  5. temperatureThe reaction mass was then cooled to 0-5° C.
  6. customquenched with H2O (5.0 mL)
  7. additionfollowed by addition of conc. HCl (0.50 mL)
  8. stirringThe resulting solution was stirred for 5 min
  9. extractionfollowed by extraction with EtOAc (3×50 mL)
  10. washThe combined organic phase was washed with brine
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified via preparative TLC

出典と根拠

ORDレコード
ord-fb460d783a724708837426ab4074aa4e
出典データセット
uspto-grants-2015_06
特許番号
US09060515B2

反応ノート

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