3-(Trifluoromethoxy)aniline → 6-methyl-N5-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N1(3-(trifluoromethoxy)phenyl)isoquinoline-1,5-diamine

HRID 2092290ノート

反応式

HRID 2092290 の反応式
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7].Cl[C:14]1[C:23]2[CH:22]=[CH:21][C:20]([CH3:24])=[C:19]([NH:25][C:26]3[C:31]([C:32]4[CH:37]=[C:36]([NH:38][CH3:39])[N:35]=[CH:34][N:33]=4)=[CH:30][CH:29]=[CH:28][N:27]=3)[C:18]=2[CH:17]=[CH:16][N:15]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.CN(C=O)C.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]>[CH3:24][C:20]1[CH:21]=[CH:22][C:23]2[C:14]([NH:7][C:6]3[CH:8]=[CH:9][CH:10]=[C:4]([O:3][C:2]([F:11])([F:12])[F:1])[CH:5]=3)=[N:15][CH:16]=[CH:17][C:18]=2[C:19]=1[NH:25][C:26]1[C:31]([C:32]2[CH:37]=[C:36]([NH:38][CH3:39])[N:35]=[CH:34][N:33]=2)=[CH:30][CH:29]=[CH:28][N:27]=1

参加物

7

反応物 4

HCID 737533-(Trifluoromethoxy)anilineHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 589422651-chloro-6-methyl-N-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)isoquinolin-5-amine

生成物 1

HCID 673414706-methyl-N5-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N1(3-(trifluoromethoxy)phenyl)isoquinoline-1,5-diamine

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 21974620tetrahydrofuran N,N-dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

3-(Trifluoromethoxy)aniline (13 μL, 96 μmol), 1-chloro-6-methyl-N-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)isoquinolin-5-amine (33 mg, 88 μmol), tris(dibenzylideneacetone)dipalladium (0) (3 mg, 4 μmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (3 mg, 7 μmol) were added to a microwave tube and suspended in THF-DMF (1:1, 1 mL). The tube was flushed with nitrogen and a solution of lithium bis(trimethylsilyl)amide, 1.0 M in hexanes (385 μL, 385 μmol) was added. The tube was heated in a microwave reactor at 150° C. for 15 min. The reaction mixture was partitioned between DCM and saturated aqueous sodium bicarbonate. The DCM layer was washed with brine, dried over sodium sulfate and concentrated. The residue was purified via preparative TLC on silica (DCM:EtOAc:EtOH:TEA=5:5:10:10) to give the desired product as a yellow solid. MS (M+H)+ 518.

後処理

  1. customThe tube was flushed with nitrogen
  2. customThe reaction mixture was partitioned between DCM and saturated aqueous sodium bicarbonate
  3. washThe DCM layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified via preparative TLC on silica (DCM:EtOAc:EtOH:TEA=5:5:10:10)

出典と根拠

ORDレコード
ord-6b0377e0bbbd476998fdc7e1f34778b3
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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