Sodium hydride → 7-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

HRID 717052Notes

Reaction equation

HRID 717052 reaction equation
[CH3:1][N:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][NH:14][C:13](=[O:18])[C:12]=3[CH:19]=2)=[CH:4][C:3]1=[O:20].[H-].[Na+].Cl.Cl[CH2:25][C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1>CN(C=O)C>[CH3:1][N:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][N:14]([CH2:25][C:26]4[N:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[C:13](=[O:18])[C:12]=3[CH:19]=2)=[CH:4][C:3]1=[O:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 200256062-(Chloromethyl)pyrimidine hydrochlorideHCID 711830677-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

Product 1

HCID 711835527-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

7-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (50 mg, 0.185 mmol) was dissolved in DMF (3 mL) and cooled down in a ice/water bath and treated with sodium hydride (60% dispersion) (17 mg, 0.41 mmol) portion wise. After 10 min a solution of 2-(chloromethyl)pyrimidine hydrochloride (37 mg, 0.22 mmol) in DMF (2 mL) was added and the reaction mixture was warmed up to room temperature and quenched with 6 mL of water after it was complete. The reaction mixture was extracted with EtOAc and water and the organic phase was dried, evaporated and purified by silica gel chromatography (95% DCM/MeOH) and then purified by reverse phase chromatography to afford 7-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one.

Workup

  1. temperaturecooled down in a ice/water bath
  2. customquenched with 6 mL of water after it
  3. extractionThe reaction mixture was extracted with EtOAc and water
  4. customthe organic phase was dried
  5. customevaporated
  6. custompurified by silica gel chromatography (95% DCM/MeOH)
  7. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-35ded4ea842941c989d65927c49d1a9c
Source dataset
uspto-grants-2015_11
Patent number
US09193694B2

Reaction notes

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