6-Chloronicotinic acid → 6-chloro-N-((7-chloro-4-oxo-1-phenyl-1,4-dihydroquinolin-3-yl)methyl)nicotinamide

HRID 1887799Notes

Reaction equation

HRID 1887799 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[NH2:20][CH2:21][C:22]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][C:27]([Cl:33])=[CH:28][CH:29]=2)[N:24]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:23]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:20][CH2:21][C:22]2[C:31](=[O:32])[C:30]3[C:25](=[CH:26][C:27]([Cl:33])=[CH:28][CH:29]=3)[N:24]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:23]=2)=[O:8])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 792226-Chloronicotinic acidHCID 81531DiisopropylethylamineHCID 712083983-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one2×

Product 1

HCID 714870636-chloro-N-((7-chloro-4-oxo-1-phenyl-1,4-dihydroquinolin-3-yl)methyl)nicotinamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 6-chloronicotinic acid (183 mg, 1.16 mmol) and N,N-diisopropylethylamine (409 mg, 552 μL, 3.16 mmol) in methylene chloride was added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphonate (BOP) (559 mg, 1.26 mmol). After 15 min., 3-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one (intermediate D) (300 mg, 1.05 mmol) was added. After 1.5 hr., the suspension was diluted with CH2Cl2 and washed with water followed by citric acid solution (5%) and finally potassium carbonate solution. The organic layer was dried, filtered and concentrated to afford 6-chloro-N-(7-chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-nicotinamide (340 mg, 76%). The product was used in subsequent reactions without further purification.

Workup

  1. waitAfter 1.5 hr
  2. washwashed with water
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-adcf8085f75849ca96f59450acc649eb
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

Loading…