4-Toluenesulfonyl chloride → 6-Chloro-4-(1-ethoxycarbonyl-piperidin-4-ylamino)2-oxo-1,2-dihydro-quinoline-3-carboxylic acid methyl ester

HRID 897231Notes

Reaction equation

HRID 897231 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[NH:7][C:8]2[C:13]([C:14]=1O)=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4].C(N(C(C)C)CC)(C)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[CH2:38]([O:40][C:41]([N:43]1[CH2:48][CH2:47][CH:46]([NH2:49])[CH2:45][CH2:44]1)=[O:42])[CH3:39]>C(#N)C.C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[NH:7][C:8]2[C:13]([C:14]=1[NH:49][CH:46]1[CH2:45][CH2:44][N:43]([C:41]([O:40][CH2:38][CH3:39])=[O:42])[CH2:48][CH2:47]1)=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4]

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 69738561Methyl 6-chloro-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate

Product 1

HCID 697369586-Chloro-4-(1-ethoxycarbonyl-piperidin-4-ylamino)2-oxo-1,2-dihydro-quinoline-3-carboxylic acid methyl esterYield 32%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-Chloro-4-hydroxy-2-oxo-1,2dihydro-quinoline-3-carboxylic acid methyl ester (445 mg, 1.8 mmol) and diisopropylethlyamine (607 uL, 3.5 mmol) in acetonitrile (30 mL) was added p-toluenesulfonyl chloride (400 mg, 2.1 mmol). The reaction was stirred at room temperature and monitored by TLC to completion (2 h). 4-amino-piperidine-1-carboxylic acid ethyl ester was then added to the reaction mixture which was stirred at 50° C. for 8 h. The reaction mixture was then diluted up with CH2Cl2 and washed with water. The organic portion was dried with MgSO4 and evaporated. The residue was purified by flash chromatography through a silica gel column with dichloromethane and methanol (95:5 v/v) to provide a white solid (235 mg, 32%) which was carried onto the next step without characterization.

Workup

  1. custommonitored by TLC to completion (2 h)
  2. stirringwas stirred at 50° C. for 8 h
  3. washwashed with water
  4. dry with materialThe organic portion was dried with MgSO4
  5. customevaporated
  6. customThe residue was purified by flash chromatography through a silica gel column with dichloromethane and methanol (95:5 v/v)

Sources & evidence

ORD record
ord-4ee168613424446aa7450eaf5cec838c
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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