Hydrochloric Acid → 6-Butoxy-2-[4-(3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-2H-isoquinolin-1-one

HRID 69423Notes

Reaction equation

HRID 69423 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[CH2:13]([O:17][C:18]1[CH:41]=[CH:40][C:21]([C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:35][CH2:34][CH:33]([N:36]([CH3:38])[CH3:37])[CH2:32]3)=[C:27]([F:39])[CH:26]=2)=[O:23])=[C:20]([CH3:42])[CH:19]=1)[CH2:14][CH2:15][CH3:16].Cl>C1COCC1.CN(C=O)C>[CH2:13]([O:17][C:18]1[CH:19]=[C:20]2[C:21](=[CH:40][CH:41]=1)[C:22](=[O:23])[N:24]([C:25]1[CH:30]=[CH:29][C:28]([N:31]3[CH2:35][CH2:34][CH:33]([N:36]([CH3:38])[CH3:37])[CH2:32]3)=[C:27]([F:39])[CH:26]=1)[CH:1]=[CH:42]2)[CH2:14][CH2:15][CH3:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 689905684-butoxy-N-[4-(3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-2-methylbenzamideHCID 178418339Butyllithium

Product 1

HCID 579167686-Butoxy-2-[4-(3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-2H-isoquinolin-1-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.6M in toluene; 0.70 mL) was added to a solution of N,N-diisopropylamine (184 mg) in THF (30 mL) at −78° C. After 10 minutes, 4-butoxy-N-[4-(3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-2-methylbenzamide (0.30 g) was added, and the mixture was stirred at −78° C. for 30 minutes and then warmed to −20° C. DMF (53 mg) was added, and the reaction mixture was hydrolyzed after a further 30 minutes with hydrochloric acid. The reaction mixture was partitioned between sodium carbonate solution and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by preparative HPLC. The product with the molecular weight of 423.54 (C25H30FN3O2) was obtained in this way; MS (ESI): 424 (M+H+).

Workup

  1. temperaturewarmed to −20° C
  2. customThe reaction mixture was partitioned between sodium carbonate solution and ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC
  6. customThe product with the molecular weight of 423.54 (C25H30FN3O2) was obtained in this way

Sources & evidence

ORD record
ord-8ba8bc138ec249ef952b5f6c4cd4fac5
Source dataset
uspto-grants-2014_09
Patent number
US08822495B2

Reaction notes

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