Sodium Carbonate → 4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridine

HRID 331021Notes

Reaction equation

HRID 331021 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.[F:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][C:24]=1B1OC(C)(C)C(C)(C)O1)[N:21]([CH3:34])[CH2:20][CH2:19]2.C(=O)([O-])[O-].[Na+].[Na+]>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:24]3[CH:23]=[C:22]4[C:18]([CH2:19][CH2:20][N:21]4[CH3:34])=[CH:17][C:16]=3[F:15])[C:3]=12

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 710896565-Fluoro-1-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 710902434-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1-isopropyl-1H-pyrrolo[2,3-b]pyridineYield 57%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 4-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine (D10) (1.500 g, 4.11 mmol), 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (1.367 g, 4.93 mmol), bis(triphenylphosphine)palladium(II) chloride (0.288 g, 0.411 mmol), 2M sodium carbonate aq. solution. (20.55 mL, 41.1 mmol) in ACN (10 mL), DMF (10 mL) and DCM (5 mL) at RT was degassed under nitrogen for 10 mins. The reaction mixture was heated to 60° C. under nitrogen atmosphere for an hour. The reaction mixture was cooled to RT and partitioned between ethyl acetate/water (ca. 50 mL each). The aqeuous layer was separated and extracted with ethyl acetate (ca. 30 mL twice). The combined organic layer was dried over MgSO4 and solvent removed in vacuo. The residue was purified using silica chromatography (eluted with 0-20% ethyl acetate/cyclohexane) to afford the title compound (910 mg). LCMS (A): m/z (M+H)+ 388/390, C19H19BrFN3 requires 387/389 (acidic).

Workup

  1. custom(20.55 mL, 41.1 mmol) in ACN (10 mL), DMF (10 mL) and DCM (5 mL) at RT was degassed under nitrogen for 10 mins
  2. temperatureThe reaction mixture was cooled to RT
  3. custompartitioned between ethyl acetate/water (ca. 50 mL each)
  4. customThe aqeuous layer was separated
  5. extractionextracted with ethyl acetate (ca. 30 mL twice)
  6. dry with materialThe combined organic layer was dried over MgSO4 and solvent
  7. customremoved in vacuo
  8. customThe residue was purified
  9. washsilica chromatography (eluted with 0-20% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-eefb4b607bed472f916d785fb1b9b7f0
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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