Dimethylformamide → 4-chloro-2-{[2-(3-fluoropyrrolidin-1-yl)ethyl]amino}-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)benzamide hydrochloride

HRID 426009Notes

Reaction equation

HRID 426009 reaction equation
Cl.[F:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7]C=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O.CS(O[CH2:25][CH2:26][NH:27][C:28]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=1[C:35](=[O:49])[NH:36][C:37]1[CH:46]=[C:45]2[C:40]([CH2:41][CH2:42][C:43](=[O:48])[N:44]2[CH3:47])=[CH:39][CH:38]=1)(=O)=O>O>[ClH:34].[Cl:34][C:32]1[CH:31]=[CH:30][C:29]([C:35]([NH:36][C:37]2[CH:46]=[C:45]3[C:40]([CH2:41][CH2:42][C:43](=[O:48])[N:44]3[CH3:47])=[CH:39][CH:38]=2)=[O:49])=[C:28]([NH:27][CH2:26][CH2:25][N:5]2[CH2:6][CH2:7][CH:3]([F:2])[CH2:4]2)[CH:33]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 578679622-({5-Chloro-2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)carbamoyl]phenyl}amino)ethyl methanesulfonateHCID 667037513-Fluoropyridine hydrochloride

Product 1

HCID 667037484-chloro-2-{[2-(3-fluoropyrrolidin-1-yl)ethyl]amino}-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)benzamide hydrochlorideYield 49.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

3-Fluoropyridine hydrochloride (240 mg) and sodium carbonate (250 mg) were added to a dimethylformamide solution of 2-({5-chloro-2-[(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)carbamoyl]phenyl}amino)ethyl methanesulfonate (595 mg), followed by stirring at 40° C. for 15 hours. Water was added to the reaction liquid, followed by extraction with chloroform. The organic layer was dried with magnesium sulfate and then the solution was concentrated under a reduced pressure. The resulting residue was purified by silica gel column chromatography (basic silica gel, chloroform:methanol, 1:0 to 95:5). By treating the resulting free base with 4 M hydrogen chloride/ethyl acetate solution, 4-chloro-2-{[2-(3-fluoropyrrolidin-1-yl)ethyl]amino}-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)benzamide hydrochloride (156 mg) was obtained as a solid.

Workup

  1. extractionfollowed by extraction with chloroform
  2. dry with materialThe organic layer was dried with magnesium sulfate
  3. concentrationthe solution was concentrated under a reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (basic silica gel, chloroform:methanol, 1:0 to 95:5)
  5. additionBy treating the resulting free base with 4 M hydrogen chloride/ethyl acetate solution

Sources & evidence

ORD record
ord-b44fb9466770414f97f15f6ddf38d92e
Source dataset
uspto-grants-2012_01
Patent number
US08106190B2

Reaction notes

Loading…