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

HRID 330996Notes

Reaction equation

HRID 330996 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:12])[CH:9]=[C:10](I)[C:3]=12.[CH3:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:21]=2)[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CN(C=O)C.C(Cl)Cl.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]([CH3:12])[CH:9]=[C:10]([C:20]3[CH:21]=[C:22]4[C:17]([CH2:16][CH2:15][N:14]4[CH3:13])=[CH:18][CH:19]=3)[C:3]=12

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 709799671-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolineHCID 710901484-bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 710903864-bromo-1-methyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridineYield 48.8%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
55 °C

Procedure

To a stirred solution of 4-bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine (D7) (5 g, 14.84 mmol) and 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (4.61 g, 17.81 mmol) in ACN (40 mL), DMF (40 mL) and DCM (20 mL) was added 2M sodium carbonate aq. solution (74.2 mL, 148 mmol). Bis(triphenylphosphine)palladium(II) chloride (1.250 g, 1.781 mmol) was then added to the solution and the resulting mixture was heated at 55° C. for ca. 1.5 hour. The reaction mixture was diluted with DCM (100 mL) and water (150 mL). The organic phase was separated and the aqueous phase was further extracted with DCM (100 mL×3). The combined organics were dried and concentrated. The residue was purified by chromatography on silica, eluting with a gradient of 0-20% ethyl acetate in cyclohexane. The corresponding fractions were combined and concentrated to give the title compound (2.48 g). LCMS (A): m/z (M+H)+ 342/344, C17H16BrN3 requires 341/343 (acidic).

Workup

  1. customThe organic phase was separated
  2. extractionthe aqueous phase was further extracted with DCM (100 mL×3)
  3. customThe combined organics were dried
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica
  6. washeluting with a gradient of 0-20% ethyl acetate in cyclohexane
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b072d1a30e0442cf89e12e65e6d0669e
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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