2-Hydroxyquinoline → HCID 69738349, compound

HRID 897217Notes

Reaction equation

HRID 897217 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:7](=[O:19])[CH:6]=[C:5]2O.[H-].[Na+].FC(F)(F)S(N(C1C=CC=CC=1)S(C(F)(F)F)(=O)=O)(=O)=O.N1C2C(=CC=CC=2)C=CC1=O.[C:55]([O:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([NH2:68])[CH2:64][CH2:63]1)=[O:61])([CH3:58])([CH3:57])[CH3:56]>C(#N)C.C(OCC)(=O)C>[C:55]([O:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([NH:68][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=3)[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[C:7](=[O:19])[CH:6]=2)[CH2:64][CH2:63]1)=[O:61])([CH3:58])([CH3:56])[CH3:57]

Participants

8

Reactant 5

HCID 60382-HydroxyquinolineHCID 24758Sodium hydrideHCID 142176Phenyl triflimideHCID 12682914-Amino-1-Boc-piperidineHCID 54684530HCID 54684530, compound

Product 1

HCID 69738349HCID 69738349, compoundYield 83.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

6-Chloro-4-hydroxy-1-pyridin-4-ylmethyl-1H-quinolin-2-one (0.891 g, 3.1 mmol) was suspended in dry acetonitrile (50 mL) under argon and treated with sodium hydride (0.14 g, 60% wt in mineral oil, 3.5 mmol). After stirring for 10 minutes, 1,1,1-trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide (1.18 g, 3.3 mmol) was added and the mixture heated to 50° C. for 1 hour. Analysis by LC/MS indicated the starting quinolone had been completely consumed and the reaction was transferred to a pressure vessel containing 4-aminopiperidine-1-carboxylic acid t-butyl ester (0.80 g, 4 mmol). The pressure vessel was sealed and heated to 100° C. for 7 hours. After cooling, the solution was diluted with ethyl acetate, washed with 1N NaOH, and dried with sodium sulfate before concentrating to give the crude product. Purification by silica chromatography using DCM and methanol eluent gave the title compound (1.22 g). 1H NMR (300 MHz, CDCl3) δ ppm 1.41 (11H, m), 2.03 (2H, m), 2.83 (2H, m), 3.50 (1H, m), 4.05 (2H, m), 5.39 (3H, m), 5.77 (1H, s), 6.87 (1H, d, J=9.04 Hz), 6.90 (2H, m), 7.23 (1H, m), 7.66 (1H, m), 8.40 (2H, m).

Workup

  1. customhad been completely consumed
  2. customthe reaction was transferred to a pressure vessel
  3. customThe pressure vessel was sealed
  4. temperatureheated to 100° C. for 7 hours
  5. temperatureAfter cooling
  6. washwashed with 1N NaOH
  7. dry with materialdried with sodium sulfate
  8. concentrationbefore concentrating
  9. customto give the crude product
  10. customPurification by silica chromatography

Sources & evidence

ORD record
ord-87e7f6e315c74e90b143d8fea949562f
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

Loading…