Sodium hydride → Ethyl 3-(3-bromobenzyl)-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

HRID 1366252Notes

Reaction equation

HRID 1366252 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([CH3:22])[N:14]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)[C:13](=[O:33])[NH:12]2)=[CH:7][CH:6]=1)#[N:4].[Br:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41]Br)[CH:36]=1>CCCCC.O1CCCC1>[Br:34][C:35]1[CH:36]=[C:37]([CH:38]=[CH:39][CH:40]=1)[CH2:41][N:12]1[CH:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]#[N:4])=[CH:6][CH:7]=2)[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([CH3:22])[N:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:32])[F:31])[CH:24]=2)[C:13]1=[O:33]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 699793-Bromobenzyl bromideHCID 10477717Ethyl 4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro5-pyrimidinecarboxylate

Product 1

HCID 59411304Ethyl 3-(3-bromobenzyl)-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (55.9 mg 1.397 mmol; 60% dispersion in mineral oil) is washed with pentane (2×10 ml) and suspended in tetrahydrofuran (10 ml). A solution of ethyl 4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (Example 4A) (500 mg, 1.164 mmol) in tetrahydrofuran (5 ml) is added with stirring. After 5 minutes at room temperature, a solution of 1-bromo-3-(bromomethyl)benzene (320 mg, 1.23 mmol) in tetrahydrofuran (5 ml) is added, and the reaction is stirred at room temperature for 16 h. The solution is quenched with water (50 ml) and extracted with ethyl acetate (3×150 ml). The combined organic phases are washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The yellow residue (approximately 1.05 g) is purified by flash chromatography over silica gel 60 (50 g) with cyclohexane/ethyl acetate (5:1) as eluent. The product is isolated as an amorphous foam.

Workup

  1. stirringthe reaction is stirred at room temperature for 16 h
  2. customThe solution is quenched with water (50 ml)
  3. extractionextracted with ethyl acetate (3×150 ml)
  4. washThe combined organic phases are washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe yellow residue (approximately 1.05 g) is purified by flash chromatography over silica gel 60 (50 g) with cyclohexane/ethyl acetate (5:1) as eluent
  9. customThe product is isolated as an amorphous foam

Sources & evidence

ORD record
ord-d9a421caf777458aa0d83d3856e8f2ca
Source dataset
uspto-grants-2011_02
Patent number
US07893073B2

Reaction notes

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