Dimethylformamide → N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

HRID 1753873Notes

Reaction equation

HRID 1753873 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10]([C:12]2[C:13]([OH:25])=[N:14][C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:16][C:17]=2[CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.[H-].[Na+].Br[CH2:34][CH2:35][O:36][CH3:37]>CCOC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10]([C:12]2[C:13]([O:25][CH2:34][CH2:35][O:36][CH3:37])=[N:14][C:15]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:16][C:17]=2[CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 178428042N-[(3-Fluorophenyl)-methyl]-2-hydroxy-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

Product 1

HCID 67286960N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amideYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 200 mg (0.58 mmol) N-[(3-Fluorophenyl)-methyl]-2-hydroxy-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (synthesis is described in section b) of example 19) in DMF (8 ml) 15 mg (0.64 mmol, 60% w/w in mineral oil) NaH were added, followed by stirring at RT for 30 min. Then 88 mg (0.64 mmol) 2-bromoethyl-methylether were added and the RM was heated to 50° C. for 16 h. Subsequently water (10 ml) and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:7) provided 90 mg (0.22 mmol, 39%) N-[(3-Fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 21). [M+H]+404.2.

Workup

  1. temperaturethe RM was heated to 50° C. for 16 h
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by CC (hexane/EtOAc 3:7)

Sources & evidence

ORD record
ord-8e6f6251548d4274a6b6cb0c5fa71806
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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