Sodium hydride → HCID 86685978, compound

HRID 2277684Notes

Reaction equation

HRID 2277684 reaction equation
[NH2:1][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.[H-].[Na+].[C:22](Cl)(=[O:26])[CH:23]([CH3:25])[CH3:24]>CN(C=O)C>[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:3]=[C:2]([NH:1][C:22](=[O:26])[CH:23]([CH3:25])[CH3:24])[CH:7]=[N:6][CH:5]=1)[CH2:17][CH2:16]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 62325Isobutyryl chlorideHCID 86685979HCID 86685979, compound

Product 1

HCID 86685978HCID 86685978, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(5-amino-pyridin-3-yl)-6-chloro-3,4-dihydro-2H-isoquinolin-1-one (27.3 mg, 0.1 mmol, example 15) in dry DMF (2 mL) was added at 0° C. NaH (3.0 mg, 0.12 mmol). The reaction mixture was allowed to stir at room temperature for 5 min before isobutyryl chloride (12.7 mg, 0.12 mmol) was added into the reaction mixture. The reaction mixture was stirred for additional 1 hour and then poured into ice-water and extracted with EtOAc (2×5 mL). The organic layer was 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 (8.1 mg, 24%) as a white solid. MS: 344.1 (M+H+).

Workup

  1. additionwas added into the reaction mixture
  2. extractionextracted with EtOAc (2×5 mL)
  3. customThe organic layer was dried over anhy
  4. filtrationNa2SO4, filtered
  5. concentrationconcentrated in vacuo
  6. customto give a crude product which
  7. customwas then purified by prep-HPLC

Sources & evidence

ORD record
ord-b83ce0ade0104290abf3728732619ee3
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

Loading…