Trifluoroacetic anhydride → Tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

HRID 386564Notes

Reaction equation

HRID 386564 reaction equation
[C:1]([C:4]1[C:9]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:8][C:7](=[O:24])[N:6]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=2)[N:5]=1)(=O)[NH2:2].C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1COCC1>[C:1]([C:4]1[C:9]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:8][C:7](=[O:24])[N:6]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:27][CH:26]=2)[N:5]=1)#[N:2]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 67446737Tert-butyl 4-(3-carbamoyl-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 44620998Tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylateYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of tert-butyl 4-(3-carbamoyl-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (985 mg, 2.0 mmol) in THF (50 mL) at room temperature under argon was added TEA (405 mg, 4.0 mmol), and was followed by addition of TFAA (840 mg, 4.0 mmol). The resulting reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The crude product was dissolved in a small amount of DCM (˜5 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes. 908 mg (91%) of tert-butyl 4-(3-cyano-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.43-1.51 (m, 9H) 1.81-1.95 (m, 2H) 1.95-2.09 (m, 2H) 3.27-3.57 (m, 2H) 3.57-3.88 (m, 2H) 4.38-4.81 (m, 1H) 6.29 (s, 1H) 7.83 (d, J=8.35 Hz, 1H) 8.20 (dd, J=8.57, 2.42 Hz, 1H) 9.04 (d, J=2.64 Hz, 1H). MS (ESI) 419 (M+H-tBu).

Workup

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. dissolutionThe crude product was dissolved in a small amount of DCM (˜5 ml)
  4. washwas eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes

Sources & evidence

ORD record
ord-e2827b90aa92410f846efd945264d1fd
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

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