1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86732148, compound

HRID 930319Notes

Reaction equation

HRID 930319 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[N:13][CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1[C@:15]1([CH2:34][F:35])[CH2:20][C@@H:19]([C:21]([F:24])([F:23])[F:22])[O:18][C:17]([NH:25]C(=O)C2C=CC=CC=2)=[N:16]1.N12CCCN=C1CCCCC2>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[N:13][CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1[C@:15]1([CH2:34][F:35])[CH2:20][C@@H:19]([C:21]([F:23])([F:24])[F:22])[O:18][C:17]([NH2:25])=[N:16]1

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86732147HCID 86732147, compound

Product 1

HCID 86732148HCID 86732148, compoundYield 56.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (85 mg, 0.173 mmol) in MeOH (690 μL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (77 μL, 0.518 mmol) dropwise. The reaction mixture was stirred at 60° C. for 1 h, then at 80° C. for another hour. After cooling to room temperature, the crude material was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 70% over 30 min. The fractions were combined and concentrated. It was partitioned between DCM and saturated NaHCO3. The aqueous layer was back extracted with DCM and the combined organic was dried (Na2SO4) and concentrated to provide (4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (38 mg, 0.098 mmol, 56.7% yield) as white solid. MS m/z=389 [M]+. Calculated for C16H13F5N4O2: 388.29.

Workup

  1. waitat 80° C. for another hour
  2. temperatureAfter cooling to room temperature
  3. customthe crude material was purified by reverse-phase preparative HPLC
  4. customover 30 min
  5. concentrationconcentrated
  6. customIt was partitioned between DCM and saturated NaHCO3
  7. extractionThe aqueous layer was back extracted with DCM
  8. dry with materialthe combined organic was dried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-0b348aecc5354825a86985dad996ec0b
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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