1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 5-(1-Methyl-1H-pyrazol-4-YL)-1H-pyrrolo[2,3-B]pyridine

HRID 1890935Notes

Reaction equation

HRID 1890935 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:11][N:12]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[N:13]1>CC(N(C)C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:11][N:12]1[CH:16]=[C:15]([C:2]2[CH:3]=[C:4]3[CH:10]=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:14]=[N:13]1

Participants

5

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 580861115-(1-Methyl-1H-pyrazol-4-YL)-1H-pyrrolo[2,3-B]pyridineYield 78%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
75 °C

Procedure

5-Bromo-1H-pyrrolo[2,3-b]pyridine (1.0 g, 5.05 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1.17 g, 5.55 mmol) and Pd(dppf)Cl2 (37 mg, 0.045 mmol) were placed in a N2 purged round-bottom flask. The reagents were dissolved in DMA (6 ml) and purged with N2. An aqueous solution of K2CO3 (978 mg in 6 ml) was then added slowly to the reaction mixture, while maintaining the temperature below 40° C., and purged for 10 minutes with N2. The solution was then heated to 75° C. overnight. Heating was discontinued and 12 ml of H2O was added. The solution was then heated to 60° C. for 1 h. Next, the solution was transferred to a separatory funnel and extracted with dichloromethane (100 ml×2). The organic layer was dried over Na2SO4 and concentrated down onto silica gel. The reaction mixture was purified by flash chromatography using a gradient of 0-10% methanol/di-chloromethane to afford 780 mg of 5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine (78% yield): 1H NMR (DMSO-d6) δ 3.94 (3H, s), 6.49 (1H, d), 7.38 (1H, d), 7.84 (1H, s), 7.97 (1H, s), 8.12 (1H, d), 8.38 (1H, d); MS (m/z) 199 [M+H]+.

Workup

  1. custompurged with N2
  2. additionAn aqueous solution of K2CO3 (978 mg in 6 ml) was then added slowly to the reaction mixture
  3. temperaturewhile maintaining the temperature below 40° C.
  4. custompurged for 10 minutes with N2
  5. temperatureHeating
  6. addition12 ml of H2O was added
  7. temperatureThe solution was then heated to 60° C. for 1 h
  8. customNext, the solution was transferred to a separatory funnel
  9. extractionextracted with dichloromethane (100 ml×2)
  10. dry with materialThe organic layer was dried over Na2SO4
  11. concentrationconcentrated down onto silica gel
  12. customThe reaction mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-c9e99b5261654d98992547ea23ac035d
Source dataset
uspto-grants-2013_08
Patent number
US08507489B2

Reaction notes

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