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

HRID 1668953노트

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HRID 1668953 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

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 microwave 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 Chromatography. (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.

후처리

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

출처 및 근거

ORD 기록
ord-e21bcbe71d7e4ef4b37f0b90b19de52a
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989461B2

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