Hydrochloric Acid → HCID 58382225, compound

HRID 1628111Notes

Reaction equation

HRID 1628111 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([CH2:11][CH3:12])=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([CH3:24])[O:23][CH2:22][CH2:21][O:20]4)=[CH:15][CH:14]=3)[N:8]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:5]2=[N:6][CH:7]=1.[CH3:33][OH:34].[Li+].[OH-:36].Cl>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:33]([OH:36])=[O:34])[N:3]=2)[N:8]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:9]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([CH3:24])[O:23][CH2:22][CH2:21][O:20]2)=[CH:15][CH:14]=1)[CH3:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 58381973HCID 58381973, compound

Product 1

HCID 58382225HCID 58382225, compoundYield 49.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 2-bromo-7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (2.00 g, 3.86 mmol, Preparation #5) and PdCl2(PPh3)2 (0.406 g, 0.579 mmol) in DMF (25 mL) was degassed under reduced pressure and the solution was placed under an atmosphere of CO. MeOH (4.70 mL, 116 mmol) and TEA (2.15 mL, 15.4 mmol) were added and then the mixture was degassed under reduced pressure and the solution placed under an atmosphere of CO. The mixture was then heated to 95° C. under an atmosphere of CO maintained via a balloon for 6.5 h. The solvents were evaporated under reduced pressure then the material was dissolved in 1,4-dioxane (50 mL). Water (10 mL) and LiOH (0.65 g, 27 mmol) were added then the mixture was heated to 75° C. for 90 min. The mixture was cooled to rt and then most of the 1,4-dioxane was removed under reduced pressure. The mixture was treated with water (50 mL) and Et2O (50 mL). The layers were separated then the organic layer was extracted with water (4×50 mL). The combined aqueous extracts were acidified with aqueous HCl (5.0 N, 6.2 mL, 31 mmol) and then extracted with DCM (50 mL, 2×30 mL). The organics were combined and dried over anhydrous MgSO4 then filtered and concentrated under reduced pressure to give 7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-2-carboxylic acid (0.92 g, 49%): LC/MS (Table 2, Method a) Rt=2.63 min; MS m/z 484 (M+H)+.

Workup

  1. customwas degassed under reduced pressure
  2. customthe mixture was degassed under reduced pressure
  3. temperaturemaintained via a balloon for 6.5 h
  4. customThe solvents were evaporated under reduced pressure
  5. dissolutionthe material was dissolved in 1,4-dioxane (50 mL)
  6. temperaturethe mixture was heated to 75° C. for 90 min
  7. temperatureThe mixture was cooled to rt
  8. custommost of the 1,4-dioxane was removed under reduced pressure
  9. additionThe mixture was treated with water (50 mL) and Et2O (50 mL)
  10. customThe layers were separated
  11. extractionthe organic layer was extracted with water (4×50 mL)
  12. extractionextracted with DCM (50 mL, 2×30 mL)
  13. dry with materialdried over anhydrous MgSO4
  14. filtrationthen filtered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3c27d0692b7945f6ba4d9161e0760f73
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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