Trifluoroacetic acid → 3-amino-4-chloro-5-(1,1-dioxidotetrahydro-2H-isothiazolo[2,3-a]pyrazin-5(3H)-yl)benzonitrile

HRID 921951Notes

Reaction equation

HRID 921951 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([C:14]#[N:15])[CH:11]=[C:10]([N:16]2[CH2:21][CH2:20][N:19]3[S:22](=[O:26])(=[O:25])[CH2:23][CH2:24][CH:18]3[CH2:17]2)[C:9]=1[Cl:27])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[C:12]([CH:11]=[C:10]([N:16]2[CH2:21][CH2:20][N:19]3[S:22](=[O:26])(=[O:25])[CH2:23][CH2:24][CH:18]3[CH2:17]2)[C:9]=1[Cl:27])[C:14]#[N:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131734958tert-butyl (2-chloro-5-cyano-3-(1,1-dioxidotetrahydro-2H-isothiazolo[2,3-a]pyrazin-5(3H)-yl)phenyl)carbamate

Product 1

HCID 1182534933-amino-4-chloro-5-(1,1-dioxidotetrahydro-2H-isothiazolo[2,3-a]pyrazin-5(3H)-yl)benzonitrileYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl-(2-chloro-5-cyano-3-(1,1-dioxidotetrahydro-2H-isothiazolo[2,3-a]pyrazin-5(3H)-yl)phenyl)carbamate (70 mg, 0.164 mmol) in DCM (1 mL) was treated with TFA (0.240 mL, 3.12 mmol) at room temperature for 2 h. Solvent was evaporated and the residue was diluted with dichloromethane and washed with saturated sodium bicarbonate. The aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 0-5% methanol/dichloromethane). 3-amino-4-chloro-5-(1,1-dioxidotetrahydro-2H-isothiazolo[2,3-a]pyrazin-5(3H)-yl)benzonitrile (37 mg) was obtained as a yellow solid.

Workup

  1. customSolvent was evaporated
  2. additionthe residue was diluted with dichloromethane
  3. washwashed with saturated sodium bicarbonate
  4. extractionThe aqueous layer was extracted with dichloromethane two more times
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude product was purified by flash chromatography on silica gel using
  9. washan automated ISCO system (24 g column, eluting with 0-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-441ffde92e9f4d21af46737e67d76276
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…