Ammonium Chloride → 3'-Fluoro-4'-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

HRID 1674294Notes

Reaction equation

HRID 1674294 reaction equation
Cl.[C:2]([NH2:5])(=[NH:4])[CH3:3].C[O-].[Na+].[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH:24]([C:30](=O)[CH2:31][CH2:32][CH3:33])[C:25](OCC)=[O:26])=[C:19]([F:35])[CH:18]=1)#[N:10].[Cl-].[NH4+]>CO.C(OCC)(=O)C>[F:35][C:19]1[CH:18]=[C:17]([C:12]2[C:11]([C:9]#[N:10])=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:22]=[CH:21][C:20]=1[CH2:23][C:24]1[C:25](=[O:26])[NH:5][C:2]([CH3:3])=[N:4][C:30]=1[CH2:31][CH2:32][CH3:33]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 67170Acetamidine monohydrochlorideHCID 10942334Sodium MethoxideHCID 57460949Ethyl 2-[(2'-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoate

Product 1

HCID 1360269433'-Fluoro-4'-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrileYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of acetamidine hydrochloride (2.67 g) in methanol (50 ml) was added sodium methoxide (28% in methanol, 8.2 mL) dropwise, followed by addition of a solution of ethyl 2-[(2′-cyano-3-fluorobiphenyl-4-yl)methyl]-3-oxohexanoate (5.18 g) in methanol (20 ml) at room temperature. After being stirred at room temperature for 15 hr, ethyl acetate and saturated aqueous ammonium chloride solution were added. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was successively washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting solid was collected and washed with diisopropyl ether to give the title compound as a white solid (3.97 g, 78%).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was successively washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting solid was collected
  7. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-e9a539e0ce70435fb75ed5d1bef1d163
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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