Trifluoroacetic acid → 3-Amino-4-chloro-5-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)benzonitrile

HRID 921943Notes

Reaction equation

HRID 921943 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[CH2:27][CH2:26][C:19]3([C:23](=[O:24])[N:22]([CH3:25])[CH2:21][CH2:20]3)[CH2:18][CH2:17]2)[C:9]=1[Cl:28])(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[CH2:27][CH2:26][C:19]3([C:23](=[O:24])[N:22]([CH3:25])[CH2:21][CH2:20]3)[CH2:18][CH2:17]2)[C:9]=1[Cl:28])[C:14]#[N:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 130364299Tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate

Product 1

HCID 899231433-Amino-4-chloro-5-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)benzonitrileYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl-(2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate (336 mg, 0.802 mmol) in DCM (3 mL) was treated with TFA (1.174 mL, 15.24 mmol) at room temperature for 2 h. Solvent was evaporated and the residue was redissolved in DCM and concentrated again. The reaction mixture 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 (40 g column, eluting with 0-10% methanol/dichloromethane). 3-amino-4-chloro-5-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)benzonitrile (179 mg) was obtained as alight yellow oil.

Workup

  1. customSolvent was evaporated
  2. dissolutionthe residue was redissolved in DCM
  3. concentrationconcentrated again
  4. additionThe reaction mixture was diluted with dichloromethane
  5. washwashed with saturated sodium bicarbonate
  6. extractionThe aqueous layer was extracted with dichloromethane two more times
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography on silica gel using
  11. washan automated ISCO system (40 g column, eluting with 0-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-cdb17ae3868e4fa9874c5c68b6c32494
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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