Isobutyric Acid → HCID 86685977, compound

HRID 2277683Notes

Reaction equation

HRID 2277683 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([Cl:18])[CH:14]=3)[C:9]2=[O:19])[CH:5]=[N:6][CH:7]=1.[CH3:20][N:21]1[CH:25]=[C:24]([CH3:26])[CH:23]=[N:22]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(O)(=O)C(C)C>CN1C(=O)CCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[Cl:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:19])[N:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:25]3[N:21]([CH3:20])[N:22]=[CH:23][C:24]=3[CH3:26])[CH:3]=1)[CH2:17][CH2:16]2

Participants

8

Reactant 4

HCID 6590Isobutyric AcidHCID 1368361,4-DimethylpyrazoleHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86685975HCID 86685975, compound

Product 1

HCID 86685977HCID 86685977, compoundYield 9.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-(5-bromo-pyridin-3-yl)-6-chloro-3,4-dihydro-2H-isoquinolin-1-one (example 7) (80 mg, 0.25 mmol) and 1,4-dimethyl-1H-pyrazole (23 mg, 0.25 mmol) in NMP (2.0 mL) were added Pd(OAc)2 (2.0 mg, 0.008 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (DavePhos) (6.3 mg, 0.016 mmol), Bu4NOAc (153 mg, 0.5 mmol) and isobutyric acid (0.085 mL, 0.08 mmol). The resulting reaction mixture was heated to 100° C. for 6 hours before it was poured into H2O (25 mL) and extracted with EtOAc (2×90 mL). The combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give title compound (8.7 mg, 9.9%) as a yellow solid. MS: 353.1 (M+H+).

Workup

  1. customThe resulting reaction mixture
  2. extractionextracted with EtOAc (2×90 mL)
  3. washThe combined organic layers were washed with brine
  4. customdried over anhy
  5. filtrationNa2SO4, filtered
  6. concentrationconcentrated in vacuo
  7. customto give a crude product which
  8. customwas then purified by prep-HPLC

Sources & evidence

ORD record
ord-e8204cb54dde47eebeb4880ba7e2cd04
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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