반응 #172018

반응 방정식

tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate

5-amino-3-methylisothiazole hydrochloride

BINAP

K2CO3

→

titled compound

수율 74.2%

4-((1R,2S)-2-aminocyclohexylamino)-5-fluoro-2-(3-methylisothiazol-5-ylamino)benzamide

수율 74.2%

용매

dioxane

반응 조건

후처리

1. 1
   기타was degassed with Ar
2. 2
   여과After the mixture was filtered
3. 3
   농축the filtrate was concentrated in vacuo
4. 4
   workup.ADDITIONTo a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added
5. 5
   workup.STIRRINGAfter being stirred at room temperature for 3 h
6. 6
   workup.ADDITIONwater and EtOAc were added
7. 7
   기타The organic phase was separated
8. 8
   건조dried over Na2SO4
9. 9
   농축concentrated in vacuo
10. 10
    workup.DISSOLUTIONThe residue was dissolved in TFA (5 mL)
11. 11
    workup.WAITAfter 30 min of standing
12. 12
    기타TFA was removed in vacuo
13. 13
    기타The residue was purified by HPLC

실험 절차

A mixture of tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate (220 mg, 0.534 mmol), 5-amino-3-methylisothiazole hydrochloride (97 mg, 0.644 mmol), BINAP (50 mg, 0.080 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (250 mg, 1.81 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 120 C for 18 h. After the mixture was filtered, the filtrate was concentrated in vacuo. To a solution of the residue in EtOH (2 mL) and DMSO (0.5 mL), 1N aq. NaOH (0.5 mL) and H2O2 (50% aq., 0.5 mL) were added. After being stirred at room temperature for 3 h, water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was dissolved in TFA (5 mL). After 30 min of standing, TFA was removed in vacuo. The residue was purified by HPLC to give the titled compound (144 mg). MS 364.4 (M+H); UV 204.7, 292.8 nm

출처