Isocyanate → 1-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-1,2-dihydro pyrido[2,3-b]pyrazin-8-yloxy)phenyl)urea

HRID 217807Notes

Reaction equation

HRID 217807 reaction equation
[N-]=C=O.[O:4]=[C:5]1[CH:10]=[N:9][C:8]2[N:11]=[CH:12][CH:13]=[C:14]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:29])OC(C)(C)C)=[CH:18][CH:17]=3)[C:7]=2[NH:6]1.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]=C=O)=[CH:33][C:32]=1[C:40]([F:43])([F:42])[F:41]>FC(F)(F)C(O)=O>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][C:23]([NH:22][C:19]2[CH:20]=[CH:21][C:16]([O:15][C:14]3[C:7]4[NH:6][C:5](=[O:4])[CH:10]=[N:9][C:8]=4[N:11]=[CH:12][CH:13]=3)=[CH:17][CH:18]=2)=[O:29])=[CH:33][C:32]=1[C:40]([F:41])([F:42])[F:43]

Participants

5

Reactant 3

HCID 105034IsocyanateHCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 46900750Tert-butyl 4-(2-oxo-1,2-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenylcarbamate

Product 1

HCID 441335461-(4-Chloro-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-1,2-dihydro pyrido[2,3-b]pyrazin-8-yloxy)phenyl)ureaYield 5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Method F1 (one pot deprotection of Boc and coupling with isocyanate): Tert-butyl 4-(2-oxo-1,2-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenylcarbamate (0.240 g, 0.67 mmol) is dissolved in trifluoroacetic acid (2 ml) and the solution is stirred at room temperature under Argon atmosphere for 2 h. The solvent is evaporated under reduced pressure and the resulting dark oil is dissolved in THF (3 ml) and triethylamine (1 ml). 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene (0.180 g, 0.80 mmol) is added in one portion, and the solution was stirred overnight at 45 C under Ar atmosphere. The solution is then cooled and evaporated and the crude was crystallised from dichloromethane and diethyl ether to afford the title compound (15 mg, 5% yield) as a brown solid.

Workup

  1. customThe solvent is evaporated under reduced pressure
  2. dissolutionthe resulting dark oil is dissolved in THF (3 ml)
  3. stirringthe solution was stirred overnight at 45 C under Ar atmosphere
  4. temperatureThe solution is then cooled
  5. customevaporated
  6. customthe crude was crystallised from dichloromethane and diethyl ether

Sources & evidence

ORD record
ord-9908a6de0df4477c80afabca2077f275
Source dataset
uspto-grants-2012_06
Patent number
US08198279B2

Reaction notes

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