Hydrogen Peroxide → HCID 86344888, compound

HRID 1503977Notes

Reaction equation

HRID 1503977 reaction equation
[CH3:1][N:2]([CH2:26][C:27](=[O:33])[N:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1)[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][CH2:23][C:24]#[N:25])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1.[OH:34][Li].O.OO>CO>[CH3:1][N:2]([CH2:26][C:27](=[O:33])[N:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1)[CH:3]1[CH2:4][CH2:5][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][CH2:23][C:24]([NH2:25])=[O:34])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 68110058HCID 68110058, compound

Product 1

HCID 86344888HCID 86344888, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A 25-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was charged with a solution of 3-[(3S)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile (80 mg, 0.17 mmol, 1.00 equiv) in methanol (5 mL) and cooled to 0° C. Then LiOH.H2O (22 mg, 0.52 mmol, 3.00 equiv) and H2O2 (30%, 0.3 mL) were added at 0° C. and the resulting solution was stirred for 2 h at the same temperature. The reaction was quenched by the addition of saturated aqueous Na2SO3 and extracted DCM. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 16 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired 3-[(3S)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide (82.5 mg) as a white solid. MS (ES): m/z 486 [M+H]+; 1H NMR (400 MHz, CD3OD): δ 8.47 (1H, s), 5.32-5.22 (1H, m), 3.58 (2H, t), 3.45 (2H, t), 3.35 (2H, s), 3.20-3.09 (1H, m), 3.03-2.95 (1H, m), 2.73-2.65 (2H, m), 2.37 (3H, s), 2.33-2.19 (5H, m), 2.03-1.88 (6H, m), 1.66 (2H, m), 1.69-1.52 (4H, m).

Workup

  1. customA 25-mL round-bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was quenched by the addition of saturated aqueous Na2SO3
  4. extractionextracted DCM
  5. washThe organic phase was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by preparative HPLC under the following conditions (SHIMADZU)
  9. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 16 min)
  10. customThe product-containing fractions were collected
  11. custompartially evaporated
  12. customto remove water and CH3CN under reduced pressure
  13. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-f2aeef44528c44dcb348f30a131cc85b
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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