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

HRID 717047Notes

Reaction equation

HRID 717047 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][NH:8][C:7](=[O:12])[C:6]=2[CH:13]=1.[H-].[Na+].Cl.Cl[CH2:18][C:19]1[N:24]=[CH:23][CH:22]=[CH:21][N:20]=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([CH2:18][C:19]3[N:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[C:7](=[O:12])[C:6]=2[CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 200256062-(Chloromethyl)pyrimidine hydrochlorideHCID 601249727-Bromo-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one

Product 1

HCID 711834087-bromo-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

7-Bromo-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (1.0 g, 4.13 mmol) was dissolved in DMF (10 ml) cooled down in a ice/water bath and treated with sodium hydride (60% dispersion) (363 mg, 9.08 mmol) portion wise. After 10 min a solution of 2-(chloromethyl)pyrimidine hydrochloride (813 mg, 4.96 mmol) in DMF (4 ml) was added, the reaction mixture warmed up to room temperature and quenched with 12 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) to afford 7-bromo-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 12 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)

Sources & evidence

ORD record
ord-d171abbe95704791ba2fdc9906ac4f6c
Source dataset
uspto-grants-2015_11
Patent number
US09193694B2

Reaction notes

Loading…