1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(6-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

HRID 930312Notes

Reaction equation

HRID 930312 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C@:18]3([CH3:40])[CH2:23][C@@H:22]([C:24]([F:27])([F:26])[F:25])[O:21][C:20]([NH:28]C(=O)C4C=CC([N+]([O-])=O)=CC=4)=[N:19]3)[N:12]=2)=[O:9])=[N:6][CH:7]=1.N12CCCN=C1CCCCC2>CO>[NH2:28][C:20]1[O:21][C@H:22]([C:24]([F:25])([F:27])[F:26])[CH2:23][C@:18]([C:13]2[N:12]=[C:11]([NH:10][C:8](=[O:9])[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=3)[CH:16]=[CH:15][C:14]=2[F:17])([CH3:40])[N:19]=1

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 867321385-chloro-N-(5-fluoro-6-((4S,6S)-4-methyl-2-(4-nitrobenzamido)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)pyridin-2-yl)picolinamide

Product 1

HCID 78321127N-(6-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamideYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

To a suspension of 5-chloro-N-(5-fluoro-6-((4S,6S)-4-methyl-2-(4-nitrobenzamido)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)pyridin-2-yl)picolinamide (8b, 76 mg, 0.131 mmol) in MeOH (1.3 mL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (Aldrich, 254 μl, 1.701 mmol). The reaction mixture was stirred at 70° C. for 1 h. The reaction was diluted with MeOH and 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 16 min. The product containing fractions were combined and neutralized with aqueous saturated sodium bicarbonate solution. The free-based product was extracted with DCM. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure to afford the title compound as a white solid (39 mg, 12% yield over two steps). MS m/z=432 [M+H]+. Calculated for C17H14ClF4N5O2: 431.

Workup

  1. custompurified by reverse-phase preparative HPLC
  2. customover 16 min
  3. additionThe product containing fractions
  4. extractionThe free-based product was extracted with DCM
  5. dry with materialThe organic phase was dried over MgSO4
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-582f0030d4df4c55ac174341832d297d
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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