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

HRID 330997Notes

Reaction equation

HRID 330997 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10](I)[C:3]=12.[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22](B3OC(C)(C)C(C)(C)O3)[CH:23]=2)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CN(C=O)C.C(Cl)Cl.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]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10]([C:22]3[CH:23]=[C:24]4[C:19]([CH2:18][CH2:17][N:16]4[CH3:15])=[CH:20][CH:21]=3)[C:3]=12

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 709799671-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolineHCID 710903694-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 710903934-bromo-1-isopropyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridineYield 68.2%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
55 °C

Procedure

To a stirred suspension of 4-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine (D10) (2.5 g, 6.85 mmol) and 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (2.130 g, 8.22 mmol) in ACN (15 mL), DMF (15.00 mL) and DCM (7.50 mL) was added 2M sodium carbonate aq. solution (34.2 mL, 68.5 mmol). Bis(triphenylphosphine)palladium(II) chloride (0.577 g, 0.822 mmol) was then added to the solution and the resulting mixture was heated at 55° C. for ca. 1 hour. Temperature was raised to 65° C. and heated for another 1 hour. The reaction was allowed to cool to RT and diluted with DCM (70 mL). The organic layer was separated and the aqueous layer was extracted with DCM (2×50 mL). The combined organics were dried and concentrated down. The residue obtained was purified on silica using 0-10% ethyl acetate/cyclohexane to afford the title compound (1.73 g). LCMS (A): m/z (M+H)+ 370/372, C19H20BrN3 requires 369/371 (acidic).

Workup

  1. temperatureTemperature was raised to 65° C.
  2. temperatureheated for another 1 hour
  3. temperatureto cool to RT
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with DCM (2×50 mL)
  6. customThe combined organics were dried
  7. concentrationconcentrated down
  8. customThe residue obtained
  9. customwas purified on silica using 0-10% ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-7e274f34a4b24296b445c4a88b963b77
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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