Methyl chloroformate → {4-[5-(4-Fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}carbamic acid methyl ester

HRID 1094499Notes

Reaction equation

HRID 1094499 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:26][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([NH2:33])[N:28]=4)=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)=[O:15])=[CH:9][C:8]=1[C:34]([F:37])([F:36])[F:35]>C(Cl)Cl.N1C=CC=CC=1.CCOC(C)=O.O>[CH3:5][O:4][C:2](=[O:3])[NH:33][C:29]1[N:28]=[C:27]([O:26][C:22]2[CH:23]=[CH:24][C:25]3[C:20](=[CH:19][CH:18]=[CH:17][C:16]=3[C:14](=[O:15])[NH:13][C:10]3[CH:11]=[CH:12][C:7]([F:6])=[C:8]([C:34]([F:37])([F:36])[F:35])[CH:9]=3)[CH:21]=2)[CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 2

HCID 6586Methyl chloroformateHCID 160715501-Naphthalenecarboxamide, 6-[(2-amino-4-pyrimidinyl)oxy]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-

Product 1

HCID 23652794{4-[5-(4-Fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}carbamic acid methyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

126 μl (1.64 mMol) methyl chloroformate are added portionwise to a solution of 300 mg (0.68 mMol) 6-(2-amino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (Step 10.3) in 7 ml CH2Cl2 and 7 ml pyridine during 2 h. After 4 h, the solution is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Precipitation with DIPE and filtration gives the title compound: m.p.: 204-205° C.

Workup

  1. customthe aq. phase separated off
  2. extractionextracted twice with EtOAc
  3. washThe organic layers are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPrecipitation
  7. filtrationwith DIPE and filtration

Sources & evidence

ORD record
ord-e66b5c88c3dc4ce3be9732cbb719bacd
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

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