Dimethylformamide → 5-Chloro-N-({1-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-4-yl}methyl)-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxamide

HRID 2425746Notes

Reaction equation

HRID 2425746 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:16]([OH:18])=O)[C:6](=[O:15])[N:7]2[CH:12]([CH3:14])[CH3:13].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2([OH:45])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)[CH2:34][CH2:33]1>ClCCl>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:16]([NH:30][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]3([OH:45])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH2:34][CH2:33]1)=[O:18])[C:6](=[O:15])[N:7]2[CH:12]([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 592550572H-Pyran-4-ol, 4-[[4-(aminomethyl)-1-piperidinyl]methyl]tetrahydro-HCID 598224655-Chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Product 1

HCID 533569805-Chloro-N-({1-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-4-yl}methyl)-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxamideYield 78.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (111 mg, 0.418 mmol, step 4 in preparation 1) in dichloromethane (1 mL) was added oxalyl chloride (0.11 mL, 1.26 mmol) and a drop of N,N-dimethylformamide at 0° C. The mixture was stirred at room temperature for 0.5 h. The solvent and excess amount of oxalyl chloride was removed in vacuo. The residue was dissolved in dichloromethane (1 mL), 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-ol (191 mg, 0.837 mmol, step 2) was added at 0° C. and the mixture was stirred at room temperature for 1 h. Then, the mixture was quenched with water (10 mL), and the aqueous layer was extracted with dichloromethane (20 mL×2). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was crystallized from isopropanol to give 156 mg (78%) of the title compound as a white solid.

Workup

  1. customat 0° C
  2. customThe solvent and excess amount of oxalyl chloride was removed in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  4. stirringthe mixture was stirred at room temperature for 1 h
  5. customThen, the mixture was quenched with water (10 mL)
  6. extractionthe aqueous layer was extracted with dichloromethane (20 mL×2)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was crystallized from isopropanol

Sources & evidence

ORD record
ord-bc9606f6f1154b50b54613730784891d
Source dataset
uspto-grants-2011_06
Patent number
US07964727B2

Reaction notes

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