Oxalyl chloride → HCID 58128704, compound

HRID 2088471Notes

Reaction equation

HRID 2088471 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:13]([C:14](O)=[O:15])=[CH:12][N:11]([CH3:17])[C:10](=[O:18])[NH:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:22])=O>CN(C=O)C.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:13]([C:14]([Cl:22])=[O:15])=[CH:12][N:11]([CH3:17])[C:10](=[O:18])[NH:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chloride2×HCID 58128676HCID 58128676, compound

Product 1

HCID 58128704HCID 58128704, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 10 mL dichloromethane and 1 drop of DMF was added 150 mg of (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid. To this mixture was added 70 μl oxalyl chloride. When the bubbling stopped another drop of oxalyl chloride was added but as no bubbling was observed the solution was stirred at room temperature for 30 minutes after which the solvent was removed in vacuo to afford crude (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid chloride (not shown in Scheme H). This acid chloride was taken up in propionitrile and added to a solution of 125 mg 5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenylamine, 3 ml propionitrile, and 0.1 ml di-iso-propylethylamine. The solution was stirred at room temperature for 18 hours, then diluted with ethyl acetate and aqueous pH 2 buffer. The layers were separated and the organic layer dried over Na2SO4, filtered and the solvent removed in vacuo to give (S)-4-(4-fluoro-phenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid{5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenyl}-amide, which was used directly in the next step without further purification.

Workup

  1. additionwas added but as no bubbling
  2. customwas removed in vacuo

Sources & evidence

ORD record
ord-8d3456a8ce6b42a982615961dbcda019
Source dataset
uspto-grants-2013_05
Patent number
US08435990B2

Reaction notes

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