Lithium Hexamethyldisilazide → 6-Methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine

HRID 2092272

反応式

HRID 2092272 の反応式
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH2:23].Cl[C:25]1[C:30]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][N:32]=2)=[CH:29][CH:28]=[CH:27][N:26]=1.CN(C1C=CC=CC=1C1C=CC=CC=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>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].C1COCC1>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=3)=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:23][C:25]1[C:30]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][N:32]=2)=[CH:29][CH:28]=[CH:27][N:26]=1

参加物

7

反応物 4

HCID 2733832Lithium HexamethyldisilazideHCID 3016205(1,1'-Biphenyl)amine, N,N-dimethyl-HCID 161089744-(2-Chloropyridin-3-yl)pyrimidineHCID 444789036-methyl-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine

生成物 1

HCID 162149046-Methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine収率 56.4%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

6-Methyl-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine (0.100 g, 0.30 mmol), 4-(2-chloropyridin-3-yl) pyrimidine (0.057 g, 0.30 mmol), dicyclohexylphosphino)-N,N-dimethylaminobiphenyl (0.0094 g, 0.024 mmol), and Pd2(dba)3 (0.010 g, 0.012 mmol) were all placed in a sealed tube containing 5 mL of anhydrous THF. Lithium bis(trimethylsilyl)amide (1.0 M in THF, 0.90 mL, 0.90 mmol) was then added to the mixture and nitrogen was bubbled into the reaction mixture for 5 min. The tube was capped and the reaction heated to 70° C. overnight. The reaction was allowed to cool to room temperature and quenched with methanol. The volatiles were removed in vacuo. The residue was taken up in ethyl acetate and washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and the purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes to give 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)-N1-(3-(trifluoromethyl)phenyl)isoquinoline-1,5-diamine as a yellow solid (80 mg, 56%). MS (M H)+ 473.

後処理

  1. customall placed in a sealed tube
  2. customwas bubbled into the reaction mixture for 5 min
  3. customThe tube was capped
  4. temperatureto cool to room temperature
  5. customquenched with methanol
  6. customThe volatiles were removed in vacuo
  7. washwashed (2×) with an aqueous saturated solution of sodium bicarbonate
  8. dry with materialThe organic layer was then dried with sodium sulfate
  9. customthe purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes

出典と根拠

ORDレコード
ord-321a583b13fd42c3bf62fc350d816103
出典データセット
uspto-grants-2013_05
特許番号
US08440674B2

関連ノート

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