Hydrochloric Acid → HCID 58539042, compound

HRID 1675944Notes

Reaction equation

HRID 1675944 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](B(O)O)[CH:7]=1.[C:11](=[O:14])([O-])[O-:12].[Cs+].[Cs+].O.[CH3:18][C:19]1[CH:23]=[CH:22][NH:21][N:20]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[OH-].[K+].Cl>CN(C)C=O.O1CCOCC1.C1COCC1.CO.C(OCC)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:2]2[CH:3]=[N:4][C:5]([N:21]3[CH:22]=[CH:23][C:19]([CH3:18])=[N:20]3)=[C:6]([C:11]([OH:12])=[O:14])[CH:7]=2)[CH:5]=[N:4][CH:3]=1

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 962WaterHCID 10796Cesium carbonateHCID 14797Potassium HydroxideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27627085-Methylpyridine-3-boronic acidHCID 178428694HCID 178428694, compound

Product 1

HCID 58539042HCID 58539042, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of methyl 2-chloro-5-iodonicotonate (5-1, 10.85 g, 36.5 mmol) in dimethylformamide (150 mL) at 25° C. was added 3-methyl-5-pyridylboronic acid (5.0 g, 36.5 mmol), PdCl2dppf (2.67 g, 3.65 mmol) followed by cesium carbonate (41.6 g, 128 mmol) and water (6.57 mL, 365 mmol) and the system was stirred for 4 h at 25° C. The system was partitioned between water and EtOAc, and dried over magnesium sulfate. Filtration and concentration yielded a brown oil which upon purification via normal phase chromatography (0→100% EtOAc in Hx) afforded a brown semi-solid which was then tritirated with MeOH and diethylether to yield a dark tan powder. To this tan powder (0.5 g, 1.9 mmol) in dioxane (13 mL) was added 3-methylpyrazole (0.47 g, 5.7 mmol) and NaHMDS (1.9 mL, 3.81 mmol) and the system was heated to 125° C. for 20 minutes in the microwave reactor. The reaction contents were partitioned between water and EtOAc followed by purification via normal phase chromatography (20→100% EtOAc in Hx) to yield a clear oil. To this clear oil (0.31 g, 1.0 mmol) in THF (2.5 mL) and MeOH (2.5 mL) was added KOH (2.0 mL, 2.0 mmol) and stirred at 135° C. for 10 minutes in a microwave reactor. The system was then acidified using 6 N HCl to a pH of 2.0 and the solvents were azeotroped off with toluene to afford the title compound (5-2) as a bone powder. ESI+MS [M+H]+ C16H14N4O2=295.1.

Workup

  1. customThe system was partitioned between water and EtOAc
  2. dry with materialdried over magnesium sulfate
  3. filtrationFiltration and concentration
  4. customyielded a brown oil which
  5. customupon purification via normal phase chromatography (0→100% EtOAc in Hx)
  6. customafforded a brown semi-solid which
  7. customto yield a dark tan powder
  8. temperaturethe system was heated to 125° C. for 20 minutes in the microwave reactor
  9. customThe reaction contents
  10. customwere partitioned between water and EtOAc
  11. customfollowed by purification via normal phase chromatography (20→100% EtOAc in Hx)
  12. customto yield a clear oil
  13. stirringstirred at 135° C. for 10 minutes in a microwave reactor
  14. customthe solvents were azeotroped off with toluene

Sources & evidence

ORD record
ord-a050b8812c8c4447ae9df929e73c8f99
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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