Sodium Carbonate → 6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

HRID 2092311ノート

反応式

HRID 2092311 の反応式
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH2:12])=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:13][C:14]1[C:19]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:18][CH:17]=[CH:16][N:15]=1.Br[C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=1[CH3:37].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:29]3[CH:30]=[C:31]([C:33]([F:34])([F:36])[F:35])[CH:32]=[CH:27][C:28]=3[CH3:37])=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:13][C:14]1[C:19]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

参加物

9

反応物 5

HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27793762-Bromo-1-methyl-4-(trifluoromethyl)benzeneHCID 589422576-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

生成物 1

HCID 673386246-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
140 °C

実験手順

To 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine (0.040 g, 0.12 mmol), charged to a 5 mL mircowave reaction vessel, 2-bromo-1-methyl-4-(trifluoromethyl)benzene (0.044 g, 0.18 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.016 g, 0.027 mmol), cesium carbonate (0.056 g, 0.17 mmol), and tris(dibenzylideneacetone)dipalladium (o) (0.011 g, 0.012 mmol) were added. The reagents were then suspended in dioxane (2.0 mL). The reaction mixture was stirred at 140° C. for 1 hrs. The reaction mixture was cooled and diluted with excess EtOAc, and partioned with aqueous sodium carbonate. The aqueous layer was back extracted 2× EtOAc. The combined organics were washed with brine, dried with magnesium sulfate and concentrated under vacuum. The resulting residue was loaded on to silica and purified by column Chromatgraphy. (ISCO 40.0 g, 0.5-5% MeOH in DCM, 30 min.) to give 6-methyl-N1-(2-methyl-5-(trifluoromethyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine as a solid after treatment with diethyl ether. MS (M+H)+ 487.

後処理

  1. additionwere added
  2. temperatureThe reaction mixture was cooled
  3. extractionThe aqueous layer was back extracted 2× EtOAc
  4. washThe combined organics were washed with brine
  5. dry with materialdried with magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. custompurified by column Chromatgraphy

出典と根拠

ORDレコード
ord-540c2f3904244ddc9b08cc112c12a89a
出典データセット
uspto-grants-2013_05
特許番号
US08440674B2

反応ノート

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