Hydrochloric Acid → 5-cyano-3-methyl-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide hydrochloride hydrate

HRID 2196361Notes

Reaction equation

HRID 2196361 reaction equation
[NH2:1][C:2]1[CH2:7][O:6][CH2:5][C@:4]([C:11]2[CH:12]=[C:13]([NH:18][C:19]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([C:28]#[N:29])=[CH:23][N:22]=3)=[O:20])[CH:14]=[CH:15][C:16]=2[F:17])([CH:8]([F:10])[F:9])[N:3]=1.C(#N)C.[ClH:33]>O>[OH2:6].[ClH:33].[NH2:1][C:2]1[CH2:7][O:6][CH2:5][C@:4]([C:11]2[CH:12]=[C:13]([NH:18][C:19]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([C:28]#[N:29])=[CH:23][N:22]=3)=[O:20])[CH:14]=[CH:15][C:16]=2[F:17])([CH:8]([F:10])[F:9])[N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 58118873N-[3-[(3R)-5-Amino-3-(difluoromethyl)-3,6-dihydro-2H-1,4-oxazin-3-yl]-4-fluorophenyl]-5-cyano-3-methyl-2-pyridinecarboxamide

Product 1

HCID 666658535-cyano-3-methyl-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide hydrochloride hydrateYield 142.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

2.3 g of 5-cyano-3-methyl-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide (5.702 mml) was put in a 4neck flask. In an Erlenmeyer flask 92 ml acetonitrile and 4.6 ml water were added. The mixture was shaken for a few seconds and 561.6 mg of HCl 37% (5.702 mmol) were added. The solution was shaken again for a few seconds and then it was added to the 4neck flask in portions. The mixture was stirred with a paddle and it was heated in a water bath up to 85° C. At 85° C. all the solid material was completely dissolved and a slightly yellow clear solution was obtained. The solution was left at rt to cool down with stirring. Precipitate appeared at 40° C. The suspension was let to stir overnight and it was filtered after 16 hours through a Büchner filter. The isolated material was dried in an oven at rt for 16 h and 1854.5 mg of a white powder was obtained.

Workup

  1. stirringThe solution was shaken again for a few seconds
  2. additionit was added to the 4neck flask in portions
  3. stirringThe mixture was stirred with a paddle and it
  4. dissolutionAt 85° C. all the solid material was completely dissolved
  5. customa slightly yellow clear solution was obtained
  6. waitThe solution was left at rt
  7. temperatureto cool down
  8. stirringwith stirring
  9. customappeared at 40° C
  10. stirringto stir overnight
  11. filtrationit was filtered after 16 hours through a Büchner
  12. filtrationfilter
  13. customThe isolated material was dried in an oven at rt for 16 h

Sources & evidence

ORD record
ord-52217fd2d9de485fbb50453752d78522
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

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