Dichloromethane → HCID 46880330, compound

HRID 661122Notes

Reaction equation

HRID 661122 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:15][C:14]([NH:16][C:17](=O)OC(C)(C)C)=[N:13][CH:12]=3)[CH:9]=2)[CH:4]=[N:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl.[C:33](O)([C:35]([F:38])([F:37])[F:36])=O>CN(C=O)C.CCOC(C)=O.Cl>[NH2:1][C@@H:10]([CH2:9][C:8]1[CH:11]=[CH:12][C:33]([C:35]([F:38])([F:37])[F:36])=[CH:6][CH:7]=1)[CH2:17][NH:16][C:14]1[S:15][C:11]([C:8]2[CH:9]=[C:10]3[C:5]([CH:4]=[N:3][CH:2]=[N:1]3)=[CH:6][CH:7]=2)=[CH:12][N:13]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 86613780HCID 86613780, compound

Product 1

HCID 46880330HCID 46880330, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred orange mixture of tert-butyl 5-(quinazolin-7-yl)thiazol-2-ylcarbamate (22 mg, 67 μmol) and Cs2CO3 (44 mg, 134 μmol) in DMF (1.0 mL), was slowly added a solution of the cyclic sulfamidate (38 mg, 100 μmol) in DMF (0.5 mL) at 50° C. The resulting light yellow mixture was stirred at 50° C. for 30 minutes. The mixture was then cooled to 0° C. and was then diluted with EtOAc and 1N HCl(aq) and the entire mixture was stirred at room temperature for 30 minutes. The layers were separated, the aqueous layer was extracted with EtOAc (5 mL×3), and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue, which was taken up in a solution of DCM (1.5 mL), and TFA (1.5 mL) was slowly added. The overall solution was stirred at room temperature for 30 minutes and concentrated. The crude residue was dissolved in DCM and mixed with silica. The solvent was evaporated, and the residue was purified with flash column chromatography (pure DCM-10% MeOH in DCM) to obtain N—((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(quinazolin-7-yl)thiazol-2-amine (12 mg, 42%) as a yellow solid.

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. stirringthe entire mixture was stirred at room temperature for 30 minutes
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (5 mL×3)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give the crude residue, which
  9. additionwas slowly added
  10. stirringThe overall solution was stirred at room temperature for 30 minutes
  11. concentrationconcentrated
  12. dissolutionThe crude residue was dissolved in DCM
  13. additionmixed with silica
  14. customThe solvent was evaporated
  15. customthe residue was purified with flash column chromatography (pure DCM-10% MeOH in DCM)

Sources & evidence

ORD record
ord-22707883773b40149c5ab14544580c3c
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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