Sodium Carbonate → 4-bromo-1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 331011Notes

Reaction equation

HRID 331011 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:13])[C:9]([CH3:12])=[C:10](I)[C:3]=12.[CH3:14][N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:22]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.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>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:13])[C:9]([CH3:12])=[C:10]([C:21]3[CH:22]=[C:23]4[C:18]([CH2:17][CH2:16][N:15]4[CH3:14])=[CH:19][CH:20]=3)[C:3]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 709799671-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolineHCID 710903404-bromo-3-iodo-1,2-dimethyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 710901424-bromo-1,2-dimethyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridineYield 15.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 4-bromo-3-iodo-1,2-dimethyl-1H-pyrrolo[2,3-b]pyridine (D27) (580 mg, 1.653 mmol) in ACN (9 mL) was added 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (557 mg, 2.148 mmol), bis(triphenylphosphine)palladium(II) chloride (116 mg, 0.165 mmol) and 9 mL of sodium carbonate (2N aqueous solution). The reaction mixture was stirred at 65° C. for 3 hours. The reaction mixture was diluted with water (30 mL), the aqueous layer was then extracted with ethyl acetate (50 mL×3). The organic layers were combined, passed through a hydrophobic frit and concentrated. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0-30% ethyl acetate in cyclohexane to give an impure material which was further purified by column chromatography on silica gel, eluting with a gradient of 0-20% ethyl acetate in cyclohexane to afford the title compound (89 mg). LCMS (A): m/z (M+H)+ 356/358, C18H18BrN3 requires 355/357 (acidic).

Workup

  1. extractionthe aqueous layer was then extracted with ethyl acetate (50 mL×3)
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography on silica gel
  4. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane
  5. customto give an impure material which
  6. customwas further purified by column chromatography on silica gel
  7. washeluting with a gradient of 0-20% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-3520dd137c9e4525a1a168bfa85db422
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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