Ethyl Acetate → 8-chloro-7-methoxy-4-(4-methoxy-benzyloxy)-2-(3-trifluoromethyl-1H-pyrazol-1-yl)-quinoline

HRID 925957Notes

Reaction equation

HRID 925957 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3]1[CH:7]=[CH:6][NH:5][N:4]=1.[H-].[Na+].Cl[C:13]1[CH:22]=[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:20]2[C:15](=[C:16]([Cl:35])[C:17]([O:33][CH3:34])=[CH:18][CH:19]=2)[N:14]=1.CCOC(C)=O>CN(C=O)C>[Cl:35][C:16]1[C:17]([O:33][CH3:34])=[CH:18][CH:19]=[C:20]2[C:15]=1[N:14]=[C:13]([N:5]1[CH:6]=[CH:7][C:3]([C:2]([F:9])([F:8])[F:1])=[N:4]1)[CH:22]=[C:21]2[O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 18070343-(Trifluoromethyl)pyrazoleHCID 566051532,8-Dichloro-7-methoxy-4-(4-methoxy-benzyloxy)-quinoline

Product 1

HCID 566051548-chloro-7-methoxy-4-(4-methoxy-benzyloxy)-2-(3-trifluoromethyl-1H-pyrazol-1-yl)-quinolineYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of compound 233a (821 mg, 1.1 eq.) in anhydrous DMF (20 mL) at 0° C. was added NaH (241 mg, 1.1 eq.) portionwise. After the reaction mixture was stirred for 1 hr at room temperature, compound 221d (2 g, 1 eq.) was added and the mixture was stirred at 90° C. for 16 hrs. After the reaction mixture was cooled to room temperature, EtOAc was added. The organic phase was washed with HCl (2.5 N), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by chromatography on silica gel (petroleum ether/DCM, 50/50) to give compound 234a as a white solid in 51% yield. MS (ESI, EI+): m/z=461.9 (MH−).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hrs
  2. temperatureAfter the reaction mixture was cooled to room temperature
  3. washThe organic phase was washed with HCl (2.5 N)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by chromatography on silica gel (petroleum ether/DCM, 50/50)

Sources & evidence

ORD record
ord-ec8dec77ea514cbab751e6986325349e
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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