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

HRID 1668932노트

반응식

HRID 1668932 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 21974620tetrahydrofuran N,N-dimethylformamide용매

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온도
150 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a05ea31ca99645bcbafcf13164a8d392
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989461B2

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