4-(Chloromethyl)benzoyl chloride → 4-chloromethyl-N-[2,4-dichloro-3-(1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-phenyl]-benzamide

HRID 270697Notes

Reaction equation

HRID 270697 reaction equation
[NH2:1][C:2]1[C:3]([Cl:21])=[C:4]([C:9]2[C:10](=[O:20])[N:11]([CH3:19])[C:12]3[C:17]([CH:18]=2)=[CH:16][N:15]=[CH:14][CH:13]=3)[C:5]([Cl:8])=[CH:6][CH:7]=1.[Cl:22][CH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>ClCCl.CCOC(C)=O>[Cl:22][CH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([C:9]3[C:10](=[O:20])[N:11]([CH3:19])[C:12]4[C:17]([CH:18]=3)=[CH:16][N:15]=[CH:14][CH:13]=4)[C:3]=2[Cl:21])=[O:29])=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 701364-(Chloromethyl)benzoyl chlorideHCID 598338933-(3-amino-2,6-dichloro-phenyl)-1-methyl-1H-[1,6]naphthyridin-2-one

Product 1

HCID 598339014-chloromethyl-N-[2,4-dichloro-3-(1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-phenyl]-benzamideYield 73.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(3-amino-2,6-dichloro-phenyl)-1-methyl-1H-[1,6]-naphthyridin-2-one (30 mg, 0.0937 mmol) in the dichloromethane (7 mL) is added 4-(chloromethyl)benzoyl chloride (53.2 mg, 0.28 mmol). After the mixture is stirred 24 hours at room temperature, it is diluted with EtOAc and washed with saturated K2CO3, brine and water. The organic layer is dried, filtered and concentrated to give crude product, which is purified by flash silica gel column elute with CH2Cl2 (100%) gradient to CH2Cl2/MeOH (NH3, 2N)(95/5%) to give the titled intermediate as a solid (32.4 mg, 73.1%).

Workup

  1. washwashed with saturated K2CO3, brine and water
  2. customThe organic layer is dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give crude product, which
  6. customis purified by flash silica gel column
  7. washelute with CH2Cl2 (100%) gradient to CH2Cl2/MeOH (NH3, 2N)(95/5%)

Sources & evidence

ORD record
ord-1d13556be367482b9aa39fb91a016d1e
Source dataset
uspto-grants-2008_11
Patent number
US07449582B2

Reaction notes

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