2,6-Lutidine → HCID 86718931, compound

HRID 528985Notes

Reaction equation

HRID 528985 reaction equation
C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:16][N:17]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:18]=2[CH2:19][CH2:20][CH2:21][CH3:22])=[C:10]([C:34]([N:36]2[C@H:45]([CH2:46][O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49])[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:37]2)=[O:35])[CH:9]=1)=[O:7])(C)(C)C.N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C1COCC1>[CH2:19]([C:18]1[N:17]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:16]=[C:15]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:14]=1[C:11]1[CH:12]=[CH:13][C:8]([C:6]([OH:7])=[O:5])=[CH:9][C:10]=1[C:34]([N:36]1[C@H:45]([CH2:46][O:47][Si:48]([C:51]([CH3:53])([CH3:52])[CH3:54])([CH3:49])[CH3:50])[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37]1)=[O:35])[CH2:20][CH2:21][CH3:22]

Participants

5

Reactant 3

HCID 79372,6-Lutidine2×HCID 65367Trimethylsilyl triflate2×HCID 71062635HCID 71062635, compound

Product 1

HCID 86718931HCID 86718931, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-(4-(tert-butoxycarbonyl)-2-((S)-3-((tert-butyldimethylsilyloxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-butyl-1-phenyl-1H-pyrazole-3-carboxylate (335 mg, 0.445 mmol) in THF (5.0 mL) was added 2,6-lutidine (0.10 mL, 0.89 mmol) followed by TMS-OTf (0.121 mL, 0.668 mmol). After stirring at room temperature for 1 h, the reaction mixture was heated at 50° C. for 1 h. Additional equivalents of both 2,6-lutidine and TMS-OTf were added hourly until consumption of the starting material (6 additions). After cooling to room temperature, the reaction mixture was quenched with sat. aq. sodium bicarbonate solution. The mixture was extracted with EtOAc concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting with 0-80% EtOAc/hexanes) to give the title compound (115 mg, 37%). MS(ESI+) m/z 696.3 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated at 50° C. for 1 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was quenched with sat. aq. sodium bicarbonate solution
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (Isco 40 g column eluting with 0-80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-023fb0814dce4557adaa5f8d15c21443
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

Loading…