Ammonia → HCID 71271109, compound

HRID 1752476Notes

Reaction equation

HRID 1752476 reaction equation
Br[C:2]1[N:7]=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[C:5]([F:18])=[CH:4][CH:3]=1.[NH3:19]>C(O)CO.[Cu-]=O>[NH2:19][C:2]1[N:7]=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[C:5]([F:18])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 86689157HCID 86689157, compound

Product 1

HCID 71271109HCID 71271109, compound

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 174Ethylene GlycolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (8.73 g, 23.17 mmol) in ethylene glycol (139 ml) and aq. NH3 (w=25%, 108 ml) in an autoclave was added copper(I) oxide (497 mg, 3.47 mmol) and the mixture was warmed to 60° C. over night. After cooling to rt the mixture was extracted with EtOAc, the organic layer was washed with aq. NH3 (w=12%, 2×), the combined organic layers were washed with sat. aq. NaCl, dried with Na2SO4 and evaporated. The residue was dissolved in TBME and extracted with 1N HCl (2×). The combined aq. layers were basified by addition of solid Na2CO3 some NaCl was added and the aq. solution extracted with DCM (4×). The combined DCM extracts were dried with K2CO3 and evaporated to provide the title compound as greyish resin. The crude material was used for the next step without further purification.

Workup

  1. temperatureAfter cooling to rt the mixture
  2. extractionwas extracted with EtOAc
  3. washthe organic layer was washed with aq. NH3 (w=12%, 2×)
  4. washthe combined organic layers were washed with sat. aq. NaCl
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. dissolutionThe residue was dissolved in TBME
  8. extractionextracted with 1N HCl (2×)
  9. additionThe combined aq. layers were basified by addition of solid Na2CO3 some NaCl
  10. additionwas added
  11. extractionthe aq. solution extracted with DCM (4×)
  12. dry with materialThe combined DCM extracts were dried with K2CO3
  13. customevaporated

Sources & evidence

ORD record
ord-7bed4fd0b8d248c1b6d1e9cff2da10a8
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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