Trifluoroacetic acid → HCID 178509950、化合物

HRID 1875064ノート

反応式

HRID 1875064 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.CC(OC([N:28](C(OC(C)(C)C)=O)[C:29]1[NH:30][C:31]([C:35](O)=[O:36])=[C:32]([Cl:34])[N:33]=1)=O)(C)C.ClC1N=C(NC(OC(C)(C)C)=O)NC=1C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:95]([OH:101])([C:97]([F:100])([F:99])[F:98])=[O:96]>CN(C=O)C>[F:98][C:97]([F:100])([F:99])[C:95]([OH:101])=[O:96].[NH2:28][C:29]1[NH:30][C:31]([C:35]([NH:1][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]3[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([Cl:19])[CH:18]=3)[C:4]=2[F:20])=[O:36])=[C:32]([Cl:34])[N:33]=1

参加物

8

反応物 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 178452983HCID 178452983、化合物HCID 178454348HCID 178454348、化合物

生成物 1

HCID 178509950HCID 178509950、化合物収率 6.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.041 g, 0.131 mmol), a 50:50 mixture of 2-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-chloro-1H-imidazole-5-carboxylic acid and 4-chloro-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-imidazole-5-carboxylic acid (0.047 g, 0.131 mmol), HATU (0.060 g, 0.157 mmol) and DIPEA (0.027 ml, 0.157 mmol) in DMF (1.5 mL) was stirred at RT overnight. The reaction mixture was extracted between EtOAc and water. The organic layer was washed with water and dried over sodium sulfate. The solvent was evaporated and the crude product was dissolved in dichloromethane (2 mL) and TFA (0.5 ml, 6.49 mmol) was added. The mixture was stirred at RT overnight. The solvent was evaporated and the residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA) to give the title compound (0.007 g, 6.2%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.56 (dd, 1H), 7.41-7.52 (m, 3H), 6.66 (s, 1H), 3.73 (s, 2H), 1.88 (br. s., 2H). ES MS: m/z 454 (M+1)

後処理

  1. extractionThe reaction mixture was extracted between EtOAc and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was evaporated
  5. dissolutionthe crude product was dissolved in dichloromethane (2 mL)
  6. stirringThe mixture was stirred at RT overnight
  7. customThe solvent was evaporated
  8. customthe residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA)

出典と根拠

ORDレコード
ord-38f58573ccd4423cb6231dceca774332
出典データセット
uspto-grants-2012_11
特許番号
US08304419B2

反応ノート

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