1,4-Dioxane → HCID 59619657, compound

HRID 445669Notes

Reaction equation

HRID 445669 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][N:23]([CH2:25][CH2:26][O:27]C6CCCCO6)[CH:24]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:34])[C:8]2=[O:35])[C:4]([CH3:36])=[N:3]1.O1CCOCC1>CO>[CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][N:23]([CH2:25][CH2:26][OH:27])[CH:24]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:34])[C:8]2=[O:35])[C:4]([CH3:36])=[N:3]1

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 59620044HCID 59620044, compound

Product 1

HCID 59619657HCID 59619657, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-8-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Stage 106.1.1, 95 mg, 0.195 mmol) in MeOH (2 ml) was added dioxane 4 M (0.248 ml, 0.993 mmol) and the RM was stirred at rt for 45 min. Then the RM was evaporated, before being quenched with saturated aqueous NaHCO3 (20 ml) and extracted with DCM (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was diluted with MeOH+2 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35). The fractions containing product were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting layer was extracted with DCM, washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound as a white solid. (HPLC: tR 2.24 min (Method A); M+H=404 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.87 (s, 1H), 8.14-8.08 (m, 1H), 8.01-7.92 (m, 2H), 7.82-7.75 (m, 1H), 7.52-7.47 (m, 1H), 7.39-7.35 (m, 1H), 4.96-4.89 (m, 1H), 4.17-4.11 (m, 2H), 3.96 (s, 3H), 3.77-3.69 (m, 2H), 3.55 (s, 3H), 1.94 (s, 3H))

Workup

  1. customThen the RM was evaporated
  2. custombefore being quenched with saturated aqueous NaHCO3 (20 ml)
  3. extractionextracted with DCM (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. additionThe residue was diluted with MeOH+2 drops TFA
  9. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35)
  10. additionThe fractions containing product
  11. customwere collected together
  12. concentrationbefore being concentrated
  13. extractionThe resulting layer was extracted with DCM
  14. washwashed with brine
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. customevaporated to dryness

Sources & evidence

ORD record
ord-0a88e23060484dee8c1c0649d707019d
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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