Phosphorus oxychloride → N-[5-(2-Acetylamino-1,3-thiazol-5-yl)-2-chloropyridin-3-yl]-2,4-dimethyl-1,3-thiazole-5-carboxamide

HRID 252725Notes

Reaction equation

HRID 252725 reaction equation
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[CH:8]=[C:9]([C:14]2[S:18][C:17]([NH:19][C:20](=[O:22])[CH3:21])=[N:16][C:15]=2C)[CH:10]=[N:11][C:12]=1[Cl:13].[CH3:24][C:25]1[S:26][C:27]([C:31](O)=[O:32])=[C:28]([CH3:30])[N:29]=1>C(#N)C>[C:20]([NH:19][C:17]1[S:18][C:14]([C:9]2[CH:8]=[C:7]([NH:6][C:31]([C:27]3[S:26][C:25]([CH3:24])=[N:29][C:28]=3[CH3:30])=[O:32])[C:12]([Cl:13])=[N:11][CH:10]=2)=[CH:15][N:16]=1)(=[O:22])[CH3:21]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 736488Dimethyl-1,3-thiazole-5-carboxylic acidHCID 86244450N-[5-(5-amino-6-chloropyridin-3-yl)-4-methyl-1,3-thiazol-2-yl]acetamide

Product 1

HCID 86620401N-[5-(2-Acetylamino-1,3-thiazol-5-yl)-2-chloropyridin-3-yl]-2,4-dimethyl-1,3-thiazole-5-carboxamideYield 66.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Phosphorus oxychloride (296 mg) was added to a stirred mixture of N-[5-(5-amino-6-chloropyridin-3-yl)-4-methyl-1,3-thiazol-2-yl]acetamide (180 mg), 2,4-dimethylthiazole-5-carboxylic acid (J. Med. Chem., 1999, 42, 5064; 109 mg) and acetonitrile (10 mL) that had been heated to reflux. The resultant mixture was stirred and heated to reflux for 1 hour. The mixture was cooled to room temperature and the precipitate was collected by filtration, washed with acetonitrile and dried under vacuum. There was thus obtained the title compound (172 mg); 1H NMR Spectrum: (DMSOd6) 2.16 (s, 3H), 2.39 (s, 3H), 2.62 (s, 3H), 2.68 (s, 3H), 8.21 (s, 1H), 8.40 (s, 1H); Mass Spectrum: M+H+ 422.

Workup

  1. temperaturehad been heated to reflux
  2. temperatureheated
  3. temperatureto reflux for 1 hour
  4. filtrationthe precipitate was collected by filtration
  5. washwashed with acetonitrile
  6. customdried under vacuum

Sources & evidence

ORD record
ord-4b74942deeef43fd86d8b7d3fea23fe4
Source dataset
uspto-grants-2011_01
Patent number
US07868188B2

Reaction notes

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