Potassium Carbonate → (4S,6S)-4-(5-(6-ethynylpyridin-3-yl)-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930326Notes

Reaction equation

HRID 930326 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([C:14]#[C:15][Si](C)(C)C)=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C@:20]1([CH2:31][F:32])[CH2:25][C@@H:24]([C:26]([F:29])([F:28])[F:27])[O:23][C:22]([NH2:30])=[N:21]1.C(=O)([O-])[O-].[K+].[K+]>CO>[C:14]([C:11]1[N:10]=[CH:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C@:20]3([CH2:31][F:32])[CH2:25][C@@H:24]([C:26]([F:27])([F:28])[F:29])[O:23][C:22]([NH2:30])=[N:21]3)[CH:4]=2)=[CH:13][CH:12]=1)#[CH:15]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 86732153(4S,6S)-4-(2-fluoro-5-(6-((trimethylsilyl)ethynyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

Product 1

HCID 86732154(4S,6S)-4-(5-(6-ethynylpyridin-3-yl)-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (4S,6S)-4-(2-fluoro-5-(6-((trimethylsilyl)ethynyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.2034 g, 0.435 mmol, Example 111), potassium carbonate (0.301 g, 2.175 mmol), and MeOH (3 mL) was stirred at room temperature for 1.25 h. The reaction mixture was concentrated in vacuo, diluted with water and extracted with DCM three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography: 0-100% EtOAc/hexane in 12 min. The product was obtained as a white solid (0.16 g, 93% yield). MS m/z=396 [M+H]+. Calculated for C19H14F5N3O: 395.3.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with DCM three times
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by silica gel chromatography
  9. wait0-100% EtOAc/hexane in 12 min

Sources & evidence

ORD record
ord-aeb9a3ceb3f04a11a6a107089c85618c
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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