Sodium hydride → 4-(6-Methoxy-1-methyl-2-oxo-1,2-dihydro-quinolin-4-ylamino)-piperidine-1-carboxylic acid ethyl ester

HRID 897228Notes

Reaction equation

HRID 897228 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]([CH3:14])[C:4](=[O:15])[CH:3]=1.[H-].[Na+].C1(NS(C(F)(F)F)(=O)=O)C=CC=CC=1.[CH2:32]([O:34][C:35]([N:37]1[CH2:42][CH2:41][CH:40]([NH2:43])[CH2:39][CH2:38]1)=[O:36])[CH3:33]>CN(C=O)C.CCOC(C)=O>[CH2:32]([O:34][C:35]([N:37]1[CH2:38][CH2:39][CH:40]([NH:43][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]([CH3:14])[C:4](=[O:15])[CH:3]=2)[CH2:41][CH2:42]1)=[O:36])[CH3:33]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 680121,1,1-Trifluoro-N-phenylmethanesulfonamideHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 54697739HCID 54697739, compound

Product 1

HCID 697373304-(6-Methoxy-1-methyl-2-oxo-1,2-dihydro-quinolin-4-ylamino)-piperidine-1-carboxylic acid ethyl esterYield 12%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 4-Hydroxy-6-methoxy-1-methyl-1H-quinolin-2-one (1.8 g, 10 mmol) in DMF (30 mL) was added sodium hydride (385 mg, 10 mmol, 60% dispersion in mineral oil). After stirring for 5 minutes, N-phenyltrifluoromethanesulfonamide (3.4 g, 10 mmol) was added and the reaction was stirred and monitored by TLC to completion (20 minutes). 4-amino-piperidine-1-carboxylic acid ethyl ester was then added and the reaction mixture was heated at 60° C. over night. The reaction mixture was then diluted up with EtOAc and washed with water, NaHCO3, and brine. The organic portion was dried over MgSO4 and evaporated to afford a residue which was purified by flash chromatography through a silica gel column with dichloromethane and methanol (95:5 v/v) to provide the title compound (445 mg, 12%). 1H NMR (300 MHz, CDCl3) δ 1.27 (2H, t, J=7.11 Hz), 1.22-1.35 (2H, m), 1.40-1.55 (2H, m), 2.10-2.20 (2H, m), 2.90-3.05 (2H, m), 3.50-3.70 (1H, m), 3.64 (3H, s), 3.87 (3H, s), 4.14 (2H, q, J=7.10), 4.50 (1H, br d, J=7.3 Hz), 5.29 (1H, s), 6.95 (1H, d; J=2.31 Hz), 7.17 (1H, dd, J=2.31, 9.03 Hz), 7.30 (1H, d, J=8.94 Hz).

Workup

  1. stirringthe reaction was stirred
  2. custommonitored by TLC to completion (20 minutes)
  3. washwashed with water, NaHCO3, and brine
  4. dry with materialThe organic portion was dried over MgSO4
  5. customevaporated
  6. customto afford a residue which
  7. customwas purified by flash chromatography through a silica gel column with dichloromethane and methanol (95:5 v/v)

Sources & evidence

ORD record
ord-982b94ad50504be8be7eb8746d4e1d3a
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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