Hydrochloric Acid → N-{4-[(2-Aminopyridin-4-yl)oxy]-2-fluorophenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide monohydrochloride

HRID 2066257ノート

反応式

HRID 2066257 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[NH:18][C:19]([C:21]1([C:24](=[O:33])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:23][CH2:22]1)=[O:20])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8](C(N)=O)[CH:7]=1.O.FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.[ClH:56].C[N:58](C)C=O>N1C=CC=CC=1>[ClH:56].[NH2:58][C:8]1[CH:7]=[C:6]([O:5][C:4]2[CH:15]=[CH:16][C:17]([NH:18][C:19]([C:21]3([C:24]([NH:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[O:33])[CH2:22][CH2:23]3)=[O:20])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][N:9]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 6228DimethylformamideHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 595970164-(3-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridine-2-carboxamide

生成物 1

HCID 68691442N-{4-[(2-Aminopyridin-4-yl)oxy]-2-fluorophenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide monohydrochloride収率 54.9%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

4-(3-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridine-2-carboxamide (1.0 g) was dissolved in N,N-dimethylformamide (10 ml) under a nitrogen atmosphere, and water (0.199 ml), [bis(trifluoroacetoxy)iodo]benzene (1.96 g) and pyridine (1.07 ml) were added at room temperature in this order, followed by stirring for 33 hr. The reaction mixture was partitioned after addition of ethyl acetate (30 ml) and a 1N aqueous solution of sodium hydroxide (10 ml). The organic layer was washed with a 1N aqueous solution of sodium hydroxide (10 ml, twice) and brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The resultant residue was dissolved in ethyl acetate (10 ml), 5N hydrochloric acid (0.486 ml, 1.1 equivalents) was added under sonication. The precipitated solid was collected by filtration, washed with ethyl acetate, and dried under aeration for 1 hr. The solid was hot air-dried at 80° C. overnight to provide the titled compound as pale brown powder (559.3 mg, 54.9%).

後処理

  1. customThe reaction mixture was partitioned
  2. additionafter addition of ethyl acetate (30 ml)
  3. washThe organic layer was washed with a 1N aqueous solution of sodium hydroxide (10 ml
  4. dry with materialtwice) and brine (30 ml) in this order, and dried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. dissolutionThe resultant residue was dissolved in ethyl acetate (10 ml)
  7. filtrationThe precipitated solid was collected by filtration
  8. washwashed with ethyl acetate
  9. customdried under aeration for 1 hr
  10. customThe solid was hot air-dried at 80° C. overnight

出典と根拠

ORDレコード
ord-9fd6d4a23bff4218a2d2d2b5f81246f0
出典データセット
uspto-grants-2012_10
特許番号
US08288538B2

反応ノート

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