1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86732169, compound

HRID 930349Notes

Reaction equation

HRID 930349 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH2:27][F:28])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH:18]C(=O)C3C=CC=CC=3)=[N:9]2)[C:5]([F:29])=[CH:4][CH:3]=1.N12CCCN=C1CCCCC2.C([O-])(O)=O.[Na+]>CO>[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH2:27][F:28])[CH2:13][C@@H:12]([C:14]([F:15])([F:16])[F:17])[O:11][C:10]([NH2:18])=[N:9]2)[C:5]([F:29])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 86732168HCID 86732168, compound

Product 1

HCID 86732169HCID 86732169, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

To a 20 mL resealable vial was added N-((4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (0.500 g, 1.046 mmol), MeOH (10 mL) and finally 1,8-diazabicyclo-[5.4.0]undec-7-ene (Aldrich; 0.312 mL, 2.091 mmol). The vial was sealed and stirred at 75° C. for 2 h. The reaction mixture was poured into sat NaHCO3 and extracted with EtOAc. The combined extracts were washed with water and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 9.0% MeOH/CH2Cl2) afforded (4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine. The material still contained some impurities. MS m/z=375.8 [M+H]+. Calculated for C11H9BrF5N3O: 375.0.

Workup

  1. customThe vial was sealed
  2. additionThe reaction mixture was poured
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated onto silica
  7. customPurification by silica gel chromatography (Gradient: 0.0 to 9.0% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a0f49dbd7276497194ad519eb07f69e4
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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