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

HRID 2092290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2092290
[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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 21974620tetrahydrofuran N,N-dimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-6b0377e0bbbd476998fdc7e1f34778b3
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440674B2

Notizen zur Reaktion

Wird geladen…