Sodium hydride → methyl N-[[2-chloro-5-[2-(4-methylphenyl)-4-pyrimidinyl]phenyl]methyl]-carbamate

HRID 70241

Reaction equation

HRID 70241 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]=[CH:10]N(C)C)=[CH:4][C:3]=1[CH2:15][NH:16][C:17](=[O:20])[O:18][CH3:19].Cl.[CH3:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=[NH:28])=[CH:25][CH:24]=1.[H-].[Na+].[Cl-].[NH4+]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][N:29]=[C:27]([C:26]3[CH:30]=[CH:31][C:23]([CH3:22])=[CH:24][CH:25]=3)[N:28]=2)=[CH:4][C:3]=1[CH2:15][NH:16][C:17](=[O:20])[O:18][CH3:19]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1227534-Methylbenzene-1-carboximidamide hydrochlorideHCID 66789975methyl N-[[2-chloro-5-[3-(dimethylamino)-1-oxo-2-propen-1-yl]phenyl]methyl]carbamate2×

Product 1

HCID 68596066methyl N-[[2-chloro-5-[2-(4-methylphenyl)-4-pyrimidinyl]phenyl]methyl]-carbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To mixture of methyl N-[[2-chloro-5-[3-(dimethylamino)-1-oxo-2-propen-1-yl]phenyl]-methyl]carbamate (i.e. the product of Step A, Example 4) (0.43 g, 1.44 mmol), 4-methylbenzamidine hydrochloride (0.74 g, 4.33 mmol) and sodium hydride (0.14 g, 5.8 mmol) at 0° C. was slowly added methanol (5 mL). The reaction mixture was heated at reflux overnight. A solution of saturated ammonium chloride was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with saturated aqueous sodium carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.160 g).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. concentrationthe mixture was concentrated under reduced pressure
  4. dissolutionThe resulting residue was dissolved in ethyl acetate
  5. washwashed with saturated aqueous sodium carbonate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by medium pressure liquid chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-31d7f18f8ef84143b86cdc29dcb06c0c
Source dataset
uspto-grants-2014_09
Patent number
US08822521B2

Linked notes

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