Pyrazole → HCID 67004338, compound

HRID 2095734Notes

Reaction equation

HRID 2095734 reaction equation
[I:1][C:2]1[C:3]([O:7][CH3:8])=[N:4][NH:5][CH:6]=1.CC1C=CC(S(O[CH:20]2[CH2:29][CH2:28][C:23]3([O:27][CH2:26][CH2:25][O:24]3)[CH2:22][CH2:21]2)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].N1C=CC=N1>CN(C=O)C>[O:24]1[C:23]2([CH2:28][CH2:29][CH:20]([N:5]3[CH:6]=[C:2]([I:1])[C:3]([O:7][CH3:8])=[N:4]3)[CH2:21][CH2:22]2)[O:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 10796Cesium carbonate2×HCID 5674891,4-Dioxaspiro[4.5]decan-8-ol, 8-(4-methylbenzenesulfonate)2×HCID 178494319HCID 178494319, compound

Product 1

HCID 67004338HCID 67004338, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-iodo-3-methoxy-1H-pyrazole (0.783 g, 3.50 mmol), 1,4-dioxaspiro[4.5]dec-8-yl 4-methylbenzenesulfonate (1.20 g, 3.84 mmol), and Cs2CO3 (1.71 g, 5.24 mmol) in anhydrous degassed DMF (26.1 mL) was heated to 100° C. for 3 h. From LCMS, there was still starting material (pyrazole) therefore the reaction mixture was charged with an additional 1,4-dioxaspiro[4.5]dec-8-yl 4-methylbenzenesulfonate (0.437 g, 1.40 mmol) and Cs2CO3 (0.683 g, 2.10 mmol) and heated to 100° C. for an additional 16 h. The reaction mixture was partitioned between EtOAc (100 mL) and H2O (25 mL) and separated. The aqueous was re-extracted with EtOAc (3×) and the combined organic fractions were washed with H2O (3×25 mL), brine (1×), dried over Na2SO4, filtered and concentrated in vacuo resulting in 1.29 g of a crude orange oil/solid mixture. The crude was crystallized from MeOH and the white crystals were filtered through a fritted funnel resulting in the title compound as white crystals. 1H NMR (400 MHz, CD3OD): δ=1.63-1.74 (m, 2H), 1.81-1.89 (m, 2H), 1.98-2.07 (m, 4H), 3.87 (s, 3H), 3.91-3.99 (m, 4H), 4.00-4.09 (m, 1H), 7.48 (s, 1H). MS (ES+): m/z 365.05 [MH+]. HPLC: tR=3.98 min (polar—5 min, ZQ3).

Workup

  1. temperatureheated to 100° C. for an additional 16 h
  2. customThe reaction mixture was partitioned between EtOAc (100 mL) and H2O (25 mL)
  3. customseparated
  4. extractionThe aqueous was re-extracted with EtOAc (3×)
  5. washthe combined organic fractions were washed with H2O (3×25 mL), brine (1×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customresulting in 1.29 g of a crude orange oil/solid mixture
  10. customThe crude was crystallized from MeOH
  11. filtrationthe white crystals were filtered through a fritted funnel

Sources & evidence

ORD record
ord-c26a511841c34d02a92c7525cb717b4e
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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