Sodium hydride → 1-methyl-4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 717064Notes

Reaction equation

HRID 717064 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)=[CH:12][C:7]=2[C:6](=[O:24])[NH:5][CH2:4][C:3]1=[O:25].[H-].[Na+].Cl.Cl[CH2:30][C:31]1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1>CN(C=O)C>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([C:13]3[CH:14]=[CH:15][C:16]([O:19][C:20]([F:23])([F:21])[F:22])=[CH:17][CH:18]=3)=[CH:12][C:7]=2[C:6](=[O:24])[N:5]([CH2:30][C:31]2[N:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:4][C:3]1=[O:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 200256062-(Chloromethyl)pyrimidine hydrochlorideHCID 711831331-Methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Product 1

HCID 711833521-methyl-4-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneYield 7.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (22.9 mg, 0.065 mmol) and NaH (15.6 mg, 0.650 mmol, 10.0 equiv.) were placed in a 0.5-2 mL Smith process vial. To the vial was added DMF (0.5 mL) followed by 2-(chloromethyl)pyrimidine hydrochloride (53.9 mg, 0.327 mmol, 5 equiv.) was added at room temperature. After stirring for 50 min, reaction was quenched with AcOH. Resulting mixture was filtered and purified via preparative reverse phase HPLC to give the title compound (2.2 mg) as a clear yellow film.

Workup

  1. additionwas added at room temperature
  2. customreaction
  3. customwas quenched with AcOH
  4. customResulting mixture
  5. filtrationwas filtered
  6. custompurified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-d7a3c878047e43d6a2c7819cf73dbc32
Source dataset
uspto-grants-2015_11
Patent number
US09193694B2

Reaction notes

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