Hydrogen Peroxide → HCID 67981417, compound

HRID 1520078Notes

Reaction equation

HRID 1520078 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[N:11]=[N:12][N:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH:26]=4)=[CH:17][CH:16]=3)[CH:14]=2)=[N:2]1.[OH-:34].[Na+].OO>C1COCC1.O>[OH:34][CH:22]1[CH:21]([C:18]2[CH:17]=[CH:16][C:15]([N:13]3[CH:14]=[C:10]([C:3]4[C:4]5[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=5)[NH:1][N:2]=4)[N:11]=[N:12]3)=[CH:20][CH:19]=2)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23]1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 67981119HCID 67981119, compound

Product 1

HCID 67981417HCID 67981417, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

To a stirred solution of borane-methyl sulfide complex (587 μl of a 2.0 M solution in THF; 1.18 mmol; 1.3 eq.) in THF (6.0 mL) maintained at 0° C. under nitrogen atmosphere, was added dropwise a solution of tert-butyl 4-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}-3,6-dihydropyridine-1(2H)-carboxylate (400 mg; 0.90 mmol; 1.0 eq.) in THF (6.0 mL). The reaction mixture was stirred at RT for 12 h. Further borane-methyl sulfide complex (135 μl of a 2.00 M solution in THF; 0.27 mmol; 0.3 eq.) was added and the reaction mixture was stirred at RT for 1 more hour. The reaction mixture was then cooled down to 0° C. before the dropwise addition of NaOH (3.6 mL) followed by hydrogen peroxide (615 μl). It was then allowed to warm to RT and stir O/N. The reaction mixture was then diluted with water and extracted with DCM (four times). The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (EtOAc:heptanes, gradient from 90:10 to 40:60) to give the title compound as a white foam (90 mg, 22%). HPLC (max plot) 96.4%; Rt % 4.16 min. UPLC/MS: (MS+) 461.4, (MS−) 459.5.

Workup

  1. addition0.3 eq.) was added
  2. stirringthe reaction mixture was stirred at RT for 1 more hour
  3. temperatureto warm to RT
  4. stirringstir O/N
  5. extractionextracted with DCM (four times)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash chromatography on silica (EtOAc:heptanes, gradient from 90:10 to 40:60)

Sources & evidence

ORD record
ord-0a4d251c4cfc4284bac50986f6895c76
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

Loading…