Cesium carbonate → (2R)-2-amino-N-{5-[3-({2-[(dimethylcarbamoyl)amino]pyridin-4-yl}methyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethoxy)phenyl}-2-phenylacetamide

HRID 546579

反応式

HRID 546579 の反応式
[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4].[CH3:40][N:41]([CH3:45])[C:42]([NH2:44])=[O:43].CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:44][C:42](=[O:43])[N:41]([CH3:45])[CH3:40])[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)HCID 86629090(2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide

生成物 1

HCID 57626026(2R)-2-amino-N-{5-[3-({2-[(dimethylcarbamoyl)amino]pyridin-4-yl}methyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethoxy)phenyl}-2-phenylacetamide

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
40 °C

実験手順

To a solution of 150 mg of (2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide obtained in stage d) of Example 5a in 10 mL of dioxane are successively added, under argon, 30 mg of N,N-dimethylurea, 13 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 5 mg of palladium acetate and 280 mg of caesium carbonate. The reaction mixture is refluxed for 1 hour and then filtered, and the filtrate is concentrated under reduced pressure. The residue is taken up in 10 mL of dioxane, 5 mL of a 4N solution of hydrogen chloride in dioxane are then added and the reaction mixture is stirred at 40° C. for 1 hour. After concentrating under reduced pressure, the residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 45 mg of ((2R)-2-amino-N-{5-[3-({2-[(dimethylcarbamoyl)amino]pyridin-4-yl}methyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethoxy)phenyl}-2-phenylacetamide, the characteristics of which are as follows:

後処理

  1. temperatureThe reaction mixture is refluxed for 1 hour
  2. filtrationfiltered
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. addition5 mL of a 4N solution of hydrogen chloride in dioxane are then added
  5. concentrationAfter concentrating under reduced pressure
  6. customthe residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid)

出典と根拠

ORDレコード
ord-0885919cbf884530850917315bd0d9bb
出典データセット
uspto-grants-2011_05
特許番号
US07935819B2

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