Ethylene Glycol → HCID 86689158, compound

HRID 1752472Notes

Reaction equation

HRID 1752472 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C:28]([F:41])([F:40])[C@:29]([C:32]3[C:37]([F:38])=[CH:36][CH:35]=[C:34](Br)[N:33]=3)([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[NH3:42].C(O)CO.CO>C(OCC)(=O)C>[NH2:42][C:34]1[N:33]=[C:32]([C@:29]2([CH3:31])[C:28]([F:41])([F:40])[CH2:27][O:26][C:25]([NH:24][C:9]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:30]2)[C:37]([F:38])=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 222AmmoniaHCID 887MethanolHCID 86689156HCID 86689156, compound

Product 1

HCID 86689158HCID 86689158, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine (23.4 g, 28.8 mmol) in ammonia (173 ml, 1.21 mol, 7M in methanol) in a microwave vial was added ethylene glycol (240 ml) and methanol (240 ml). Copper oxide Cu2O (1.21 g, 8.46 mmol) was added and the vial was sealed. The reaction mixture was stirred at 80° C. for 43 hours. The cold reaction mixture was diluted with ethyl acetate and washed with water, aqueous ammonia and brine. The organic layer was dried over sodium sulfate, filtered and evaporated. The crude product was chromatographed over silica gel (400 g, dichloromethane/methanol 98:2+0.2% ammonia) to give the title compound: 4.29 g (25% yield).

Workup

  1. customthe vial was sealed
  2. customThe cold reaction mixture
  3. washwashed with water, aqueous ammonia and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was chromatographed over silica gel (400 g, dichloromethane/methanol 98:2+0.2% ammonia)

Sources & evidence

ORD record
ord-8e20aa83c6a54c54909f1db77853f66a
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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