Triethylamine → Methyl 5'-[(2-chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylate

HRID 970219Notes

Reaction equation

HRID 970219 reaction equation
ClC1C=C(C(Cl)=O)C=CN=1.[Cl:11][C:12]1[CH:13]=[C:14]([CH:35]=[CH:36][N:37]=1)[C:15]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:34])=[C:22]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:25]=2)[CH:23]=1)=[O:16].NC1C=CC(C)=C(C2C=CC(C(OC)=O)=CC=2)C=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([CH:35]=[CH:36][N:37]=1)[C:15]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:34])=[C:22]([C:24]2[CH:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:29]=2)[CH:23]=1)=[O:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 21090583Methyl 5'-amino-2'-methyl-1,1'-biphenyl-4-carboxylateHCID 86595281Methyl 5'-[(2-chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylate 2-Chloropyridine-4-carbonyl chloride

Product 1

HCID 21090582Methyl 5'-[(2-chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl 5′-[(2-chloroisonicotinoyl)amino]-2′-methyl-1,1′-biphenyl-4-carboxylate 2-Chloropyridine-4-carbonyl chloride (1.58 g, 9.0 mmol) in DCM (10 ml) was added dropwise to a solution of methyl 5′-amino-2′-methyl-1,1′-biphenyl-4-carboxylate (1.81 g, 7.5 mmol) and triethylamine (3.13 ml, 22.5 mmol) in DCM (10 ml) at 0° C. The reaction was stirred at room temperature for 20 h, the solvent evaporated under vacuum and the residue partitioned between ethyl acetate (50 ml) and saturated aqueous sodium bicarbonate (50 ml). The aqueous was extracted with ethyl acetate (50 ml) and the combined organic phases washed with brine (50 ml), dried (magnesium sulphate) and the solvent evaporated under vacuum. The residue was purified by flash column chromatography on silica eluting with DCM/ethanol/ammonia (300:8:1). The solvents were evaporated under vacuum to give methyl 5′-[(2-chloroisonicotinoyl)amino]-2′-methyl-1,1′-biphenyl-4-carboxylate (1.73 g, 61%). LCMS: retention time 3.69 min, MH+381.

Workup

  1. customthe solvent evaporated under vacuum
  2. customthe residue partitioned between ethyl acetate (50 ml) and saturated aqueous sodium bicarbonate (50 ml)
  3. extractionThe aqueous was extracted with ethyl acetate (50 ml)
  4. washthe combined organic phases washed with brine (50 ml)
  5. dry with materialdried (magnesium sulphate)
  6. customthe solvent evaporated under vacuum
  7. customThe residue was purified by flash column chromatography on silica eluting with DCM/ethanol/ammonia (300:8:1)
  8. customThe solvents were evaporated under vacuum

Sources & evidence

ORD record
ord-3b70e03dee3649fab466d4a5ad694ea3
Source dataset
uspto-grants-2007_12
Patent number
US07309800B2

Reaction notes

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