Acetamidine monohydrochloride → 3'-Chloro-4'-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

HRID 1718914Notes

Reaction equation

HRID 1718914 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]#[N:27])[CH:5]=[CH:6][C:7]=1[CH2:8][CH:9]([C:15](=O)[CH2:16][CH2:17][CH3:18])[C:10](OCC)=[O:11].Cl.[C:29](=[NH:32])([NH2:31])[CH3:30].C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:20]2[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:11])[NH:32][C:29]([CH3:30])=[N:31][C:15]=1[CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 67170Acetamidine monohydrochlorideHCID 10942334Sodium MethoxideHCID 57460890Ethyl 2-[(3-chloro-2'-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate

Product 1

HCID 1361469193'-Chloro-4'-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 60% sodium hydride (0.40 g) in tetrahydrofuran (20 mL) was added dropwise a solution of ethyl butyrylacetate (2.13 g) in tetrahydrofuran (10 mL). After stirring for 30 min, 4′-(bromomethyl)-3′-chlorobiphenyl-2-carbonitrile (2.06 g) was added. The mixture was stirred at room temperature for 15 hr, and 1 M hydrochloric acid was added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography to give ethyl 2-[(3-chloro-2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate. Then, a solution of the obtained ethyl 2-[(3-chloro-2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate, ethanimidamide hydrochloride (2.55 g), 28% sodium methoxide (7.80 g) in methanol (50 mL) was stirred overnight. The solvent was evaporated under reduced pressure, and saturated aqueous ammonium chloride solution was added to the residue. The precipitated solid was collected by filtration, and washed with water and diethyl ether to give the title compound (0.64 g, 73%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure, and saturated aqueous ammonium chloride solution
  2. additionwas added to the residue
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with water and diethyl ether

Sources & evidence

ORD record
ord-83d68dbfdb944a8eae7c35c54aae2168
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Reaction notes

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