Sodium hydride → tert.-Butyl 3-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoro-methyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}benzoate

HRID 421798Notes

Reaction equation

HRID 421798 reaction equation
[H-].[Na+].[CH:3]1([C:6]([C:8]2[CH:9]([C:26]3[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=3)[NH:10][C:11](=[O:25])[N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[C:13]=2[CH3:14])=[O:7])[CH2:5][CH2:4]1.Br[CH2:35][C:36]1[CH:37]=[C:38]([CH:46]=[CH:47][CH:48]=1)[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>CCCCC.O1CCCC1>[C:30]([C:29]1[CH:28]=[CH:27][C:26]([CH:9]2[N:10]([CH2:35][C:36]3[CH:37]=[C:38]([CH:46]=[CH:47][CH:48]=3)[C:39]([O:41][C:42]([CH3:45])([CH3:43])[CH3:44])=[O:40])[C:11](=[O:25])[N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:22])[F:23])[CH:16]=3)[C:13]([CH3:14])=[C:8]2[C:6]([CH:3]2[CH2:5][CH2:4]2)=[O:7])=[CH:33][CH:32]=1)#[N:31]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 14591193tert-Butyl 3-(bromomethyl)benzoateHCID 596848504-{5-(Cyclopropylcarbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzonitrile

Product 1

HCID 59684777tert.-Butyl 3-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoro-methyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (12.1 mg, 0.31 mmol; 60% suspension in mineral oil) is washed with pentane (3×3 ml), then treated with a solution of 4-{5-(cyclopropylcarbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzonitrile (Example 22) (100 mg, 0.235 mmol) in tetrahydrofuran (5 ml). After 5 minutes, the reaction is treated with a solution of tert.-butyl 3-(bromomethyl)benzoate (77 mg, 0.28 mmol) in tetrahydrofuran (5 ml) and then stirred at room temperature overnight (16 h). The reaction mixture 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 in vacuo. The crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 10:90→90:10).

Workup

  1. customThe reaction mixture is quenched with water (50 ml)
  2. extractionextracted with ethyl acetate (3×150 ml)
  3. washThe combined organic phases are washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 10:90→90:10)

Sources & evidence

ORD record
ord-7a6afe9c9dcf471c8125ddf8aa624b21
Source dataset
uspto-grants-2012_01
Patent number
US08101615B2

Reaction notes

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