Water → HCID 9932923, compound

HRID 388009Notes

Reaction equation

HRID 388009 reaction equation
C1(O[C:8](=[O:32])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=4)[N:20]=[CH:19][CH:18]=3)=[CH:12][C:11]=2[F:31])C=CC=CC=1.[NH2:33][C:34]1[S:35][CH:36]=[CH:37][N:38]=1.C(OCC)(=O)C.O>CS(C)=O.CO>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH3:30])[N:20]=[CH:19][CH:18]=[C:17]2[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:8]([NH:33][C:34]2[S:35][CH:36]=[CH:37][N:38]=2)=[O:32])=[C:11]([F:31])[CH:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 21552-AminothiazoleHCID 8857Ethyl Acetate2×HCID 58930897HCID 58930897, compound

Product 1

HCID 9932923HCID 9932923, compoundYield 86.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

4-(6,7-Dimethoxyquinolin-4-yloxy)-2-fluorophenylcarbamic acid phenyl ester (109 mg, 0.250 mmol) and 2-aminothiazole (50.0 mg, 0.500 mmol) were heated and stirred in dimethylsulfoxide (1 ml) at 85° C. for 2 hours. The reaction solution was distributed between ethyl acetate and water, the organic layer was washed with 1N aqueous sodium hydroxide, water and saturated saline and dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was distilled off under reduced pressure. The obtained crude product was subjected to silica gel column chromatography (eluent-ethyl acetate:methanol=30:1), the fraction containing the target substance was concentrated and suspended in ethyl acetate, the suspension was diluted with hexane and the crystals were filtered out, washed with hexane and blow-dried to obtain the title compound (95.0 mg, 0.216 mmol, 86%) as colorless crystals.

Workup

  1. washthe organic layer was washed with 1N aqueous sodium hydroxide, water and saturated saline
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationthe drying agent was filtered off
  4. distillationthe filtrate was distilled off under reduced pressure
  5. customThe obtained crude product
  6. additionthe fraction containing the target substance
  7. concentrationwas concentrated
  8. additionthe suspension was diluted with hexane
  9. filtrationthe crystals were filtered out
  10. washwashed with hexane
  11. customblow-dried

Sources & evidence

ORD record
ord-fa9b1858216b4a4ab7923fbb07a634a0
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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