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

HRID 1094503Notes

Reaction equation

HRID 1094503 reaction equation
Cl[C:2]([O:4][CH2:5][CH:6]([CH3:8])[CH3:7])=[O:3].[F:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:29][C:30]4[CH:35]=[CH:34][N:33]=[C:32]([NH2:36])[N:31]=4)=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)=[O:18])=[CH:12][C:11]=1[C:37]([F:40])([F:39])[F:38]>C(Cl)Cl.N1C=CC=CC=1.CCOC(C)=O.O>[CH2:5]([O:4][C:2](=[O:3])[NH:36][C:32]1[N:31]=[C:30]([O:29][C:25]2[CH:26]=[CH:27][C:28]3[C:23](=[CH:22][CH:21]=[CH:20][C:19]=3[C:17](=[O:18])[NH:16][C:13]3[CH:14]=[CH:15][C:10]([F:9])=[C:11]([C:37]([F:40])([F:39])[F:38])[CH:12]=3)[CH:24]=2)[CH:35]=[CH:34][N:33]=1)[CH:6]([CH3:8])[CH3:7]

Participants

7

Reactant 2

HCID 62365Isobutyl chloroformateHCID 160715501-Naphthalenecarboxamide, 6-[(2-amino-4-pyrimidinyl)oxy]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-

Product 1

HCID 23652795{4-[5-(4-Fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}carbamic acid isobutyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

110 μl (0.84 mMol) isobutyl 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 4.5 ml CH2Cl2 and 7.5 ml pyridine. After 1 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. Chromatography (Combi Flash; CH2Cl2-CH2Cl2/EtOH 19:1) gives the title compound: MS: [M+1]+=543.

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

Sources & evidence

ORD record
ord-3f2524e1b6d84e93a9a3fb39d57362f6
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

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