Trifluoroacetic anhydride → HCID 44621657, compound

HRID 386555Notes

Reaction equation

HRID 386555 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]([Cl:31])=[C:27]([Cl:32])[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]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[N:5]=1)#[N:2]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 44621629HCID 44621629, compound

Product 1

HCID 44621657HCID 44621657, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of tert-butyl 4-(3-carbamoyl-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (example 16) (9 mg, 0.019 mmol) in THF (1 mL) at room temperature under argon was added TEA (5.65 mg, 0.056 mmol), and was followed by addition of TFAA (11.73 mg, 0.056 mmol). The resulting reaction mixture was stirred at room temperature overnight. Solvent was removed in vacuo. The crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give tert-butyl 4-(3-cyano-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (6 mg, white solid, 69.2%). 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 9H) 1.74-1.94 (m, 2H) 1.92-2.12 (m, 2H) 3.32-3.55 (m, 2H) 3.58-3.81 (m, 2H) 4.42-4.72 (m, 1H) 6.26 (s, 1H) 7.45 (dd, J=8.79, 2.20 Hz, 1H) 7.55 (d, 1H) 7.72 (d, J=2.20 Hz, 1H). MS (ESI) 409 (M+H-tBu).

Workup

  1. customThe resulting reaction mixture
  2. customSolvent was removed in vacuo
  3. customThe crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA)

Sources & evidence

ORD record
ord-4ec083bd6bd64262a5aa6460cd3614f7
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

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