Triethylamine → 2,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide

HRID 922010Notes

Reaction equation

HRID 922010 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([CH3:11])[CH:5]=[C:4]([Cl:12])[N:3]=1.[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][NH2:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C1COCC1>[Cl:1][C:2]1[C:7]([C:8]([NH:18][CH2:17][C:16]2[CH:19]=[CH:20][CH:21]=[C:14]([F:13])[CH:15]=2)=[O:10])=[C:6]([CH3:11])[CH:5]=[C:4]([Cl:12])[N:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 668533-FluorobenzylamineHCID 6761212,6-Dichloro-4-methylpyridine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 866643132,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amideYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 17.4 g (84.4 mmol) of 2,6-dichloro-4-methyl-pyridine-3-carboxylic acid in THF (340 ml) were added 10.6 ml (92.9 mmol) 3-fluorobenzylamine, 32.0 g (84.4 mmol) HATU and 35.0 ml (253.3 mmol) NEt3. The RM was then heated at 70° C. for 16. After dilution with EtOAc (350 ml) the mixture was washed with a 4M aq. NH4Cl sol., a 1M aq. NaHCO3 sol. and brine. The organic layer was dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:2) provided 19.5 g (62.3 mmol, 74%) 2,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide.

Workup

  1. washAfter dilution with EtOAc (350 ml) the mixture was washed with a 4M aq. NH4Cl sol.
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by CC (hexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-7cd666d81ad34cec9d6017e67aef0234
Source dataset
uspto-grants-2016_03
Patent number
US09278103B2

Reaction notes

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