Potassium Carbonate → 7-(3-aminopyrid-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1 5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one

HRID 1754553Notes

Reaction equation

HRID 1754553 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:20]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[N:19]=[CH:18][C:7]=3[C:8](=[O:17])[N:9]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:10]=2[CH:11]=1.BrC1C=C[C:31]2[C:32]3NN(C4CCCCO4)C[C:33]=3[C:34](=O)[N:35](CC(F)(F)F)[C:36]=2C=1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB(C2C(N)=[N:69]C=CC=2)O1.C([O-])(O)=O.[Na+]>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.CN(C=O)C>[NH2:69][C:33]1[CH:34]=[N:35][CH:36]=[CH:31][C:32]=1[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:20]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[N:19]=[CH:18][C:7]=3[C:8](=[O:17])[N:9]([CH2:12][C:13]([F:14])([F:15])[F:16])[C:10]=2[CH:11]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 438110672-Aminopyridine-3-boronic acid, pinacol esterHCID 894540797-bromo-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-oneHCID 894542027-Bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one

Product 1

HCID 894541727-(3-aminopyrid-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1 5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-oneYield 88%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

7-Bromo-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-bromo-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (9.7 g, 19.4 mmol), potassium carbonate (5.3 g, 38.4 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrid-2-amine (4.82 g, 21.9 mmol), 14 mL of anhydrous DMF, 1.8 mL of degassed water, and the catalyst PdCl2(dppf) (0.79 g, 0.96 mmol) are successively introduced into a microwave reactor under argon. The reactor is sealed and the mixture is stirred for 10 minutes at 130° C. under microwave irradiation. The mixture is diluted with EtOAc, poured into saturated aqueous NaHCO3 solution and stirred for 30 minutes. The precipitate is filtered off and washed with water and then taken up in isopropanol. After filtering off and drying, 7.58 g of a grey powder are obtained (yield: 88%).

Workup

  1. customThe reactor is sealed
  2. stirringstirred for 30 minutes
  3. filtrationThe precipitate is filtered off
  4. washwashed with water
  5. filtrationAfter filtering off
  6. customdrying

Sources & evidence

ORD record
ord-955cead6f6e247a38785baea860a3041
Source dataset
uspto-grants-2015_10
Patent number
US09169246B2

Reaction notes

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