Pyrrolidine → HCID 23156768, compound

HRID 1098290Notes

Reaction equation

HRID 1098290 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[NH:50]1[CH2:54][CH2:53][CH2:52][CH2:51]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[N:50]1([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:54][CH2:53][CH2:52][CH2:51]1

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23156880HCID 23156880, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 23156768HCID 23156768, compoundYield 50.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture consisting of 500 mg (1.54 mmol) of the 7-chloro-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one prepared in Step B of Example 1; 45.0 mg (0.15 mmol) of 2-(di-t-butylphosphino)biphenyl; 17.0 mg (0.075 mmol) of palladium acetate; and 713 mg (7.42 mmol) of sodium t-butoxide, was suspended in 15 ml of toluene. Thereafter, 0.533 ml (6.39 mmol) of pyrrolidine was added to the above suspension, and the obtained mixture was then stirred under heating to reflux for 2 hours. Thereafter, the reaction solution was stood to cool, and water was then added thereto, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and was then concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:5), so as to obtain 277.9 mg (50%) of 7-pyrrolidin-1-yl-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a yellow solid.

Workup

  1. temperatureunder heating
  2. temperatureto reflux for 2 hours
  3. temperatureto cool
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. concentrationwas then concentrated
  7. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:5)

Sources & evidence

ORD record
ord-7ac3bc3d029c487f837cb4d08de69dd2
Source dataset
uspto-grants-2012_03
Patent number
US08143274B2

Reaction notes

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