Trifluoroacetic acid → 1-(4-(3-Amino-4-cyanoisothiazol-5-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea

HRID 871030Notes

Reaction equation

HRID 871030 reaction equation
[C:1]([C:3]1[C:4]([NH:26]CC2C=CC(OC)=CC=2OC)=[N:5][S:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=2[F:25])=[O:16])=[CH:10][CH:9]=1)#[N:2].FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[NH2:26][C:4]1[C:3]([C:1]#[N:2])=[C:7]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([NH:17][C:18]3[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=3[F:25])=[O:16])=[CH:10][CH:9]=2)[S:6][N:5]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 866892251-(4-{4-Cyano-3-[(2,4-dimethoxybenzyl)amino]isothiazol-5-yl}phenyl)-3-(2-fluoro-5-methylphenyl)urea

Product 1

HCID 866892261-(4-(3-Amino-4-cyanoisothiazol-5-yl)phenyl)-3-(2-fluoro-5-methylphenyl)ureaYield 94.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 1-(4-{4-cyano-3-[(2,4-dimethoxybenzyl)amino]isothiazol-5-yl}phenyl)-3-(2-fluoro-5-methylphenyl)urea (593 mg, 1.15 mmol) in 50 mL of CH2Cl2 was treated with 1.5 mL of trifluoroacetic acid. Solid was dissolved and the reaction turned to yellow and then red in color. TLC indicated the completion of the reaction in <30 min. Saturated Na2CO3 solution was added and the mixture was stirred for 30 min. Layers were separated and the aqueous layer was extracted with CH2Cl2 (3×). The combined organic extracts were washed with brine and dried with MgSO4, filtered, and concentrated. The crude product was redissolved in 100 mL of EtOAc. Insoluble impurity was filtered through celite and washed with EtOAc. Filtrate was concentrated in vacuo to afford the title compound as a cream solid (398 mg, 94%).

Workup

  1. dissolutionSolid was dissolved
  2. customthe completion of the reaction in <30 min
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe crude product was redissolved in 100 mL of EtOAc
  10. filtrationInsoluble impurity was filtered through celite
  11. washwashed with EtOAc
  12. concentrationFiltrate was concentrated in vacuo

Sources & evidence

ORD record
ord-dbf596af908f4bd6a0c61d3362cf12f4
Source dataset
uspto-grants-2015_03
Patent number
US08969583B2

Reaction notes

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