Morpholine → 6-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-2-morpholin-4-yl-pyridine-3-carboxylic acid

HRID 1753860Notes

Reaction equation

HRID 1753860 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([Cl:20])[N:3]=1.[C:21]([O-:24])([O-])=[O:22].[K+].[K+].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CN(C=O)C>[Cl:20][C:4]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH:8]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:7]([C:21]([OH:24])=[O:22])=[C:6]([CH3:19])[CH:5]=1.[Cl:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[N:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 866643132,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide

Product 2

HCID 672874356-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-2-morpholin-4-yl-pyridine-3-carboxylic acidYield 49%HCID 866643172-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amideYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2.0 g (6.4 mmol) 2,6-dichloro-N-(3-fluorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesis is described in section a) of example 2) in DMF (19 ml) were added 1.32 g (9.6 mmol) K2CO3 and 660 mg (7.7 mmol) morpholine and the RM was stirred at 90° C. for 16 h. Then the RM was poured into ice water (40 ml), followed by extraction with EtOAc (3×40 ml). The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:2) provided 1.14 g (3.2 mmol, 49%) 6-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-2-morpholin-4-yl-pyridine-3-carboxylic acid and 400 mg (1.1 mmol, 17%) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide.

Workup

  1. extractionfollowed by extraction with EtOAc (3×40 ml)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by CC (hexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-d8e191ec885346869a6c0a0941c4d696
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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