Ammonium Chloride → (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide

HRID 1929503Notes

Reaction equation

HRID 1929503 reaction equation
C([O:3][C:4]1[CH2:9][O:8][CH2:7][C:6]([C:11]2[CH:12]=[C:13]([NH:17][C:18]([C:20]3[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][N:21]=3)=[O:19])[CH:14]=[CH:15][CH:16]=2)([CH3:10])[N:5]=1)C.[Cl-].[NH4+]>CO>[CH3:10][C:6]1([C:11]2[CH:12]=[C:13]([NH:17][C:18]([C:20]3[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][N:21]=3)=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH2:7][O:8][CH2:9][C:4](=[O:3])[NH:5]1

Participants

4

Reactant 2

HCID 25517Ammonium ChlorideHCID 66931414HCID 66931414, compound

Product 1

HCID 66931532(RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amideYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A dried pressure tube was charged under an argon atmosphere with a dispersion of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(5-ethoxy-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide (0.348 g, 0.9 mmol) and ammonium chloride (0.182 g, 3.4 mmol) in methanol (10 ml). The sealed pressure tube was heated at 100° C. for 16 hours. After cooling, the reaction mixture was evaporated to dryness and directly purified by chromatography on an Isolute flash NH2 column using a gradient of dichloromethane/methanol=100/0 to 95/5 as the eluent. There were obtained 0.076 g (38% of theory) of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide (=3,5-difluoro-pyridine-2-carboxylic acid [3-((RS)-3-methyl-5-oxo-morpholin-3-yl)-phenyl]-amide) as a white solid; mass (calculated) C17H15F2N3O3 [347.324]; (found) [M+H]+=348, and 0.113 g (57% of theory) of (RS)-3,5-difluoro-pyridine-2-carboxylic acid [3-(5-amino-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide (1) as a light yellow foam; mass (calculated) C17H16F2N4O2 [346.340]; (found) [M+H]+=347.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was evaporated to dryness
  3. customdirectly purified by chromatography on an Isolute flash NH2 column

Sources & evidence

ORD record
ord-3035cebfb62042ff88898cab970b8349
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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