Acetone → HCID 46946170, compound

HRID 1047634Notes

Reaction equation

HRID 1047634 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([C@H:7]([NH:9][C:10]([C:12]2[CH:20]=[C:19]3[C:15]([C:16](C(C)=C)=[N:17][N:18]3[C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[CH:14][CH:13]=2)=[O:11])[CH3:8])[O:4][N:3]=1.C[N+]1([O-])CC[O:35]CC1.[CH3:39][C:40]([CH3:42])=[O:41]>O.[Os](=O)(=O)(=O)=O>[OH:35][CH2:39][C:40]([C:16]1[C:15]2[C:19](=[CH:20][C:12]([C:10]([NH:9][C@@H:7]([C:5]3[O:4][N:3]=[C:2]([CH3:1])[N:6]=3)[CH3:8])=[O:11])=[CH:13][CH:14]=2)[N:18]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)[N:17]=1)([OH:41])[CH3:42]

Participants

6

Reactant 3

HCID 180AcetoneHCID 82029Methyl morpholine oxideHCID 66661480HCID 66661480, compound

Product 1

HCID 46946170HCID 46946170, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent

Procedure

N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-3-(prop-1-en-2-yl)-1H-indazole-6-carboxamide (40.6 mg, 0.101 mmol) was dissolved in acetone (919 μl)/water (92 μl). N-methylmorpholine oxide (15.2 mg, 0.130 mmol) was added. Osmium tetroxide (2.5% in n-butanol, 32 μl, 2.55 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h. The reaction was stopped, quenched by addition of saturated aqueous sodium sulfite (5 mL), and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×5 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The residue was purified by preparative HPLC (reverse phase, C-18), eluting with acetonitrile/water+0.1% trifluoroacetic acid. The product fraction was diluted with ethyl acetate (15 mL), washed with saturated aqueous sodium bicarbonate (2×15 mL) and saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), and the solvent evaporated under reduced pressure to give the title compound (1:1 mixture of diastereomers) (32.9 mg, 0.076 mmol, 74.7% yield) as a white solid. HRMS: [M+1]=436.2001. 1H NMR (500 MHz, CDCl3): δ 8.15 (s, 1H); 8.00 (dd, J=8.5, 4.7 Hz, 1H); 7.53-7.46 (m, 3H); 7.30 (d, J=7.9 Hz, 2H); 7.13 (d, J=8.0 Hz, 1H); 5.58 (t, J=7.3 Hz, 1H); 4.22 (dd, J=11.3, 3.3 Hz, 1H); 3.78 (d, J=11.4 Hz, 1H); 2.42 (s, 3H); 2.45-2.28 (m, 3H); 1.71-1.65 (m, 6H).

Workup

  1. customquenched by addition of saturated aqueous sodium sulfite (5 mL)
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×5 mL)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe residue was purified by preparative HPLC (reverse phase, C-18)
  8. washeluting with acetonitrile/water+0.1% trifluoroacetic acid
  9. additionThe product fraction was diluted with ethyl acetate (15 mL)
  10. washwashed with saturated aqueous sodium bicarbonate (2×15 mL) and saturated aqueous sodium chloride (1×10 mL)
  11. dry with materialdried (sodium sulfate)
  12. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-2dcfa7b0a5164962a7614c0998e1e9f5
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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