Ammonia → HCID 66547317, compound

HRID 403273Notes

Reaction equation

HRID 403273 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C@@H:6]([NH:11][C:12]3[CH:13]=[CH:14][C:15]([F:29])=[C:16]([C@:18]4([CH3:28])[C:24]([F:26])([F:25])[CH2:23][O:22][CH2:21][C:20](=S)[NH:19]4)[CH:17]=3)[CH2:7][CH2:8][C:9]=2[CH:10]=1.CO.C(OO)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].[NH3:44]>>[NH2:44][C:20]1[CH2:21][O:22][CH2:23][C:24]([F:26])([F:25])[C@:18]([C:16]2[CH:17]=[C:12]([NH:11][C@@H:6]3[C:5]4[N:4]=[CH:3][C:2]([Cl:1])=[CH:10][C:9]=4[CH2:8][CH2:7]3)[CH:13]=[CH:14][C:15]=2[F:29])([CH3:28])[N:19]=1

Participants

6

Reactant 5

HCID 222AmmoniaHCID 887MethanolHCID 6410tert-Butyl hydroperoxideHCID 10340Sodium CarbonateHCID 88950948HCID 88950948, compound

Product 1

HCID 66547317HCID 66547317, compoundYield 45%

Conditions

Temperature
23 °C

Procedure

To a solution of (R)-5-[5-((S)-3-chloro-6,7-dihydro-5H-[1]pyrindin-7-ylamino)-2-fluoro-phenyl]-6,6-difluoro-5-methyl-[1,4]oxazepane-3-thione (intermediate A20Ab) (16 mg, 36.2 μmol) in 7 M ammonia in methanol (0.4 mL, 2.8 mmol) at 23° C. was added tert-butyl hydroperoxide (70% in water, 16.3 mg, 17.4 μL, 181 μmol) and the mixture stirred at 23° C. for 22 hours. Poured into aqueous 2 M Na2CO3 solution, extracted with ethyl acetate, the organic layer was dried over Na2SO4. Removal of the solvent in vacuum left a light brown solid, which was purified by flash chromatography (silica gel (amine)) with n-heptane/ethyl acetate to give the title compound as a yellow solid (7 mg, 45%). MS (ISP): m/z=425.1 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layer was dried over Na2SO4
  3. customRemoval of the solvent in vacuum
  4. waitleft a light brown solid, which
  5. customwas purified by flash chromatography (silica gel (amine)) with n-heptane/ethyl acetate

Sources & evidence

ORD record
ord-da13f579d8644e398c150c7ab2c8ede1
Source dataset
uspto-grants-2014_06
Patent number
US08748418B2

Reaction notes

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