Methanol → HCID 66801968, compound

HRID 1843916Notes

Reaction equation

HRID 1843916 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][N:10]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[CH3:21])[C:11]2=[O:14])=[CH:6][CH:5]=1.Cl[C:23]1[N:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]=1.CO>CN(C=O)C.C(Cl)Cl>[F:29][C:26]1[CH:25]=[N:24][C:23]([O:3][C:4]2[CH:13]=[C:12]3[C:7]([CH2:8][CH2:9][N:10]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][C:20]=4[CH3:21])[C:11]3=[O:14])=[CH:6][CH:5]=2)=[N:28][CH:27]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 5834662-Chloro-5-fluoropyrimidineHCID 56942892HCID 56942892, compound

Product 1

HCID 66801968HCID 66801968, compoundYield 10.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

60% NaH (13 mg, 0.33 mmol) was added to a stirred solution of 7-hydroxy-2-(4-methyl-pyridin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (27A: 70 mg, 0.275 mmol) in DMF (2 mL) at 0° C. The reaction mixture was stirred at room temperature for 1 hour. This was followed by the addition of 2-chloro-5-fluoro-pyrimidine (44 mg, 0.33 mmol) at 0° C. and stirring was continued for a further 1 hour at room temperature. The reaction was monitored by TLC (5% methanol in DCM). The reaction mixture was quenched with chilled water and extracted with ethylacetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (2% methanol in DCM) afforded 10 mg of the product (10.4% yield).

Workup

  1. stirringstirring
  2. waitwas continued for a further 1 hour at room temperature
  3. customThe reaction mixture was quenched with chilled water
  4. extractionextracted with ethylacetate
  5. washThe organic layer was washed with brine solution
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel (2% methanol in DCM)

Sources & evidence

ORD record
ord-a14ea3a99e744fdaab0df2e6f4172b9c
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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