HCID 58382335, compound → HCID 58382165, compound

HRID 1628115Notes

Reaction equation

HRID 1628115 reaction equation
[CH3:1][Mg]Cl.[CH2:4]([C:6]1[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[CH:11]=[N:10][C:9]=2[NH:8][C:7]=1[C:18]1[CH:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=1)[CH3:5]>C1COCC1>[CH2:4]([C:6]1[C:14]2[N:13]3[CH:15]=[CH:16][N:17]=[C:12]3[CH:11]=[N:10][C:9]=2[NH:8][C:7]=1[C:18]1[CH:23]=[CH:22][C:21]([C:24]([OH:26])([CH3:1])[CH3:25])=[CH:20][CH:19]=1)[CH3:5]

Participants

4

Reactant 2

HCID 58382335HCID 58382335, compoundHCID 178418332HCID 178418332, compound2×

Product 1

HCID 58382165HCID 58382165, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

MeMgCl (3 M in THF, 0.54 mL, 1.6 mmol) was added to THF (3 mL) then cooled to about −20° C. 1-(4-(1-Ethyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-2-yl)phenyl)ethanone (0.062 g, 0.204 mmol) was suspended in THF (3 mL) then added to the MeMgCl solution with stirring while maintaining the temperature of the mixture at about −15 to −20° C. The flask with the 1-(4-(1-ethyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-2-yl)phenyl)ethanone was rinsed with THF (2 mL) then this solution was also added to the MeMgCl mixture. The mixture was stirred for about 10 min then AcOH (1 mL) was added. The material was purified in two equal portions by preparative reverse phase HPLC (Table 2, method j). The fractions from the preparative HPLC containing the title compound were concentrated under reduced pressure to remove most or all of the 1,4-dioxane. The mixture was basified with saturated aqueous NaHCO3 and the solids collected by filtration. The material was dried overnight under vacuum at about 60° C. to give 2-(4-(1-ethyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-2-yl)phenyl)propan-2-ol (0.033 g, 51%): LC/MS (Table 2, Method a) Rt=1.85 min; MS m/z 321 (M+H)+. Syk IC50=B

Workup

  1. temperaturewhile maintaining the temperature of the mixture at about −15 to −20° C
  2. washThe flask with the 1-(4-(1-ethyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-2-yl)phenyl)ethanone was rinsed with THF (2 mL)
  3. additionthis solution was also added to the MeMgCl mixture
  4. stirringThe mixture was stirred for about 10 min
  5. additionAcOH (1 mL) was added
  6. customThe material was purified in two equal portions by preparative reverse phase HPLC (Table 2, method j)
  7. additionThe fractions from the preparative HPLC containing the title compound
  8. concentrationwere concentrated under reduced pressure
  9. customto remove most
  10. filtrationthe solids collected by filtration
  11. customThe material was dried overnight under vacuum at about 60° C.

Sources & evidence

ORD record
ord-1026f91c49c44bbd99034c0619115ea5
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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