Phenacylamine → HCID 67540673, compound

HRID 1192326Notes

Reaction equation

HRID 1192326 reaction equation
[H-].[Na+].[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](O)=[CH:5][N:4]=1.NCC(C1C=CC=CC=1)=O.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.[C:45]([N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46]>CN(C=O)C>[C:48]([O:47][C:45]([N:52]1[CH2:57][CH2:56][N:55]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:3]=[N:4][CH:5]=2)[CH2:54][CH2:53]1)=[O:46])([CH3:51])([CH3:49])[CH3:50]

Participants

7

Reactant 5

HCID 11952PhenacylamineHCID 24758Sodium hydrideHCID 142176Phenyl triflimideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178516801HCID 178516801, compound

Product 1

HCID 67540673HCID 67540673, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
40 °C

Procedure

To a suspension of NaH (60% in mineral oil, 0.099 g, 2.46 mmol) in DMF (5 mL) was added cinnolin-4-ol (prepared from 2-aminoacetophenone according to the procedures described in U.S. Pat. No. 4,620,000), 0.300 g, 2.05 mmol) in DMF (2 mL) dropwise. The reaction mixture was warmed at 40° C. and stirred for 30 minutes. After cooling, N-phenyltrifluoromethanesulfonimide (0.880 g, 2.46 mmol) in DMF (2 mL) was added, and the reaction mixture was stirred at room temperature for 1 hour. 1-Boc piperazine (0.765 g, 4.11 mmol) was added to the mixture. The reaction was stirred at 80° C. for 4 hours. After cooling, the mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with water, brine, dried and concentrated. The residue was purified by column chromatography (1:1 to 1:3 hexanes/EtOAc) to give 4-Cinnolin-4-yl-piperazine-1-carboxylic acid tert-butyl ester (0.246 g, 38%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.91 (s, 1H), 8.47 (d, J=8.4 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.80 (t, J=7.2 Hz, 1H), 7.69 (t, J=7.2 Hz, 1H), 3.74 (m, 4H), 3.34 (m, 4H), 1.51 (s, 9H). LCMS (APCI+) m/z 315 [M+H]+; Rt=2.14 minutes.

Workup

  1. temperatureAfter cooling
  2. stirringthe reaction mixture was stirred at room temperature for 1 hour
  3. stirringThe reaction was stirred at 80° C. for 4 hours
  4. temperatureAfter cooling
  5. customthe mixture was partitioned between EtOAc and water
  6. extractionThe aqueous phase was extracted with EtOAc
  7. washThe combined organic layers were washed with water, brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (1:1 to 1:3 hexanes/EtOAc)

Sources & evidence

ORD record
ord-6dd1dc720ced4799b23a6515e43653c8
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…