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

HRID 930329Notes

Reaction equation

HRID 930329 reaction equation
C([NH:9][C:10]1[O:11][C@H:12]([C:35]([F:38])([F:37])[F:36])[CH2:13][C@:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([N:27]3[CH2:32][CH2:31][CH:30]([O:33][CH3:34])[CH2:29][CH2:28]3)=[O:26])[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1)(=O)C1C=CC=CC=1.N12CCCN=C1CCCCC2>CO>[NH2:9][C:10]1[O:11][C@H:12]([C:35]([F:36])([F:38])[F:37])[CH2:13][C@:14]([C:17]2[CH:18]=[C:19]([NH:24][C:25]([N:27]3[CH2:28][CH2:29][CH:30]([O:33][CH3:34])[CH2:31][CH2:32]3)=[O:26])[CH:20]=[CH:21][C:22]=2[F:23])([CH3:16])[N:15]=1

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86732157N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide

Product 1

HCID 86732158N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamideYield 51%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of N-(3-((4S,6S)-2-benzamido-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-4-methoxypiperidine-1-carboxamide (0.166 g, 0.309 mmol) in MeOH (3 mL) at room temperature was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (0.100 mL, 0.669 mmol). The reaction was heated at 60° C. for 4 h. Then the reaction was cooled to room temperature, diluted with MeOH, purified by reverse-phase HPLC (Gilson; Gemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA CH3CN (9:1→1:9). The fractions containing the desired product were combined and concentrated in vacuo. The material was dissolved in MeOH and eluted with MeOH, through an Silicycle carbonate cartridge to give the titled compound as a white crystalline solid (68 mg, 51%). MS m/z=433 [M+H]+. Calculated for C19H24F4N4O3: 432

Workup

  1. temperatureThen the reaction was cooled to room temperature
  2. custompurified by reverse-phase HPLC (Gilson
  3. washGemini-NX 10m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O
  4. additionThe fractions containing the desired product
  5. concentrationconcentrated in vacuo
  6. dissolutionThe material was dissolved in MeOH
  7. washeluted with MeOH, through an Silicycle carbonate cartridge

Sources & evidence

ORD record
ord-da3b2fa1ef8b4e448ba0f07293efdf10
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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