Methanol → 2-Methylsulfanyl-4-(2-(phenylamino)phenylamino)pyrimidine-5-carboxylic acid (4-fluorophenyl)amide

HRID 348499Notes

Reaction equation

HRID 348499 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12](Cl)=[N:13][C:14]([S:17][CH3:18])=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.[C:20]1([NH:26][C:27]2[C:28]([NH2:33])=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CN1CCOCC1.CO>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12]([NH:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[NH:26][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[N:13][C:14]([S:17][CH3:18])=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 68297N-Phenyl-o-phenylenediamineHCID 188588054-Chloro-2-methylsulfanylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide

Product 1

HCID 867604042-Methylsulfanyl-4-(2-(phenylamino)phenylamino)pyrimidine-5-carboxylic acid (4-fluorophenyl)amideYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-chloro-2-methylsulfanylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide (100 mg, 0.34 mmol) in dichloromethane (10 mL) was added N-phenyl-benzene-1,2-diamine (148 mg, 0.4 mmol) followed by N-methylmorpholine-bound resin (300 mg). The mixture was stirred at an ambient temperature for 16 h and was then heated at reflux for an additional 2 h. Methanol (5 mL) was added and the mixture was stirred at an ambient temperature for 40 h. The mixture was filtered through a plug of celite and the filter plug was washed with hot ethyl acetate (25 mL). The resulting solution was treated with hexanes to precipitate 70 mg (0.16 mmol, 47% yield) of the titled compound as a purple-red solid. 1H NMR (300 MHz, DMSO-d6) δ 10.64 (s, 1H), 10.29 (s, 1H), 8.74 (s, 1H), 8.10 (m, 1H), 7.58 (m, 3H), 7.25–7.05 (m, 7H), 6.79–6.679(m, 3H), 2.5(s, 3H); MS (EI) m/z 444.05 (M−H)−.

Workup

  1. temperaturewas then heated
  2. temperatureat reflux for an additional 2 h
  3. stirringthe mixture was stirred at an ambient temperature for 40 h
  4. filtrationThe mixture was filtered through a plug of celite
  5. washthe filter plug was washed with hot ethyl acetate (25 mL)
  6. additionThe resulting solution was treated with hexanes

Sources & evidence

ORD record
ord-e271941b58034d948f098e0d38073e31
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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