p-Toluenesulfonic acid → 2-(5-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol-4-yl)-3-phenethyl-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1170903Notes

Reaction equation

HRID 1170903 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:9])=[C:6]([C:19]([F:22])([F:21])[F:20])[N:5]=[CH:4][CH:3]=1.[CH3:23][C:24]1[N:25]([C:30]2[S:34][CH:33]=[N:32][C:31]=2[CH:35]=O)[C:26]([CH3:29])=[CH:27][CH:28]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:23][C:24]1[N:25]([C:30]2[S:34][CH:33]=[N:32][C:31]=2[C:35]2[N:10]([CH2:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8](=[O:9])[C:7]3[C:6]([C:19]([F:22])([F:20])[F:21])=[N:5][CH:4]=[CH:3][C:2]=3[N:1]=2)[C:26]([CH3:29])=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 595538795-(2,5-Dimethyl-1H-pyrrol-1-YL)thiazole-4-carbaldehydeHCID 595538854-amino-N-phenethyl-2-(trifluoromethyl)nicotinamide

Product 1

HCID 595538992-(5-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol-4-yl)-3-phenethyl-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-oneYield 17.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 4-amino-N-phenethyl-2-(trifluoromethyl)nicotinamide (25.5 mg, 0.082 mmol), 5-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole-4-carbaldehyde (17 mg, 0.082 mmol) and TsOH (1.4 mg, 0.008 mmol) in toluene was heated at reflux overnight. The reaction was then filtered and to the crude mixture was added manganese oxide. The reaction was heated at 110° C. for 4 h. The reaction mixture was filtered, concentrated and purified with silica gel chromatography providing a solid, 2-(5-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol-4-yl)-3-phenethyl-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one (7 mg). 1H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H), 8.76 (d, 1H), 7.69 (m, 1H), 7.51 (m, 1H), 7.48 (d, 1H), 7.32 (m, 5H), 4.20 (m, 2H), 3.32 (m, 2H), 2.07 (s, 6H). MS m/z 496.5 (M+H)+.

Workup

  1. temperatureat reflux overnight
  2. filtrationThe reaction was then filtered and to the crude mixture
  3. additionwas added manganese oxide
  4. filtrationThe reaction mixture was filtered
  5. concentrationconcentrated
  6. custompurified with silica gel chromatography

Sources & evidence

ORD record
ord-0aa4247d58904a2a97ca5085ffd6de8b
Source dataset
uspto-grants-2010_11
Patent number
US07829572B2

Reaction notes

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