Ammonium Chloride → 2-{5-{[4-Butyl-1-(5-methoxypyrimidin-2-yl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}pyridin-2-yl}benzonitrile

HRID 1622976Notes

Reaction equation

HRID 1622976 reaction equation
C[Al](C)C.[NH2:5][C:6]1[N:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][N:7]=1.[C:14]([NH:17]/[C:18](/[CH2:39][CH2:40][CH2:41][CH3:42])=[C:19](/[CH2:24][C:25]1[CH:26]=[N:27][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:37]#[N:38])=[CH:29][CH:30]=1)\[C:20](OC)=[O:21])(=O)[CH3:15].[Cl-].[NH4+]>CCCCCC.C(OCC)(=O)C.C(Cl)(Cl)Cl.ClCCCl>[CH2:39]([C:18]1[N:17]=[C:14]([CH3:15])[N:5]([C:6]2[N:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][N:7]=2)[C:20](=[O:21])[C:19]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:37]#[N:38])=[N:27][CH:26]=1)[CH2:40][CH2:41][CH3:42]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 23052442-Amino-5-methoxypyrimidineHCID 16682925TrimethylaluminumHCID 86667259methyl (Z)-3-acetamido-2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-2-heptenoate

Product 1

HCID 679794502-{5-{[4-Butyl-1-(5-methoxypyrimidin-2-yl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}pyridin-2-yl}benzonitrileYield 77%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolvent2×HCID 6212ChloroformSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Process 3: Under argon atmosphere, trimethylaluminum (2 mol/L hexane solution, 1.45 mL, 2.90 mmol) was added to 1,2-dichloroethane (30 mL) solution of 2-amino-5-methoxypyrimidine (220 mg, 1.74 mmol) at room temperature, and stirred at the same temperature for 80 minutes. 1,2-dichloroethane (20 mL) solution of methyl(Z)-3-acetamido-2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-2-heptenoate (227 mg, 0.58 mmol) was added dropwise thereto at room temperature followed by reflux for 17 hours under heating. An aqueous solution of ammonium chloride and chloroform were added to the reaction mixture, which was then filtered through a pad of celite. The organic layer in the filtrate was separated, and the aqueous layer was extracted with chloroform. The organic layer was combined, washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residues obtained were subjected to silica gel column chromatography (hexane/ethyl acetate=2:1) to obtain 2-{5-{[4-butyl-1-(5-methoxypyrimidin-2-yl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}pyridin-2-yl}benzonitrile (207 mg, 77%) as a yellow oil.

Workup

  1. customat room temperature
  2. temperatureby reflux for 17 hours
  3. temperatureunder heating
  4. filtrationwas then filtered through a pad of celite
  5. customThe organic layer in the filtrate was separated
  6. extractionthe aqueous layer was extracted with chloroform
  7. washwashed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residues obtained

Sources & evidence

ORD record
ord-318796b2df0b47129e7ecb2c0dd28a47
Source dataset
uspto-grants-2014_07
Patent number
US08778954B2

Reaction notes

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