Acetonitrile → 4-bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine

HRID 331020Notes

Reaction equation

HRID 331020 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][CH:15]1[CH3:32].C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl>[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][CH:15]([CH3:32])[N:14]4[CH3:13])=[CH:18][CH:19]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 710901484-bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridineHCID 710901551,2-Dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline

Product 1

HCID 711145544-bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridineYield 46.8%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

4-Bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine (D7) (1.1 g, 3.26 mmol), 1,2-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (970 mg, 3.55 mmol), bis(triphenylphosphine) palladium(II) chloride (0.229 g, 0.326 mmol) and 2M sodium carbonate aqueous solution (16.32 mL, 32.6 mmol) were suspended in DMF (10 mL), ACN (10 mL) and DCM (5 mL). This was degassed under nitrogen for 10 mins before being heated to 70° C. and left stirring at this temperature for 30 mins. The reaction mixture was partitioned between ethyl acetate/water (ca. 40 mL each). The aqueous layer was separated and extracted with ethyl acetate (ca. 25 mL twice). The combined organic layer were dried over MgSO4 and concentrated. The residue was purified using chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to afford title compound (544 mg). LCMS (A): m/z (M+H)+ 356/358, C18H18BrN3 requires 355/357 (acidic).

Workup

  1. customThis was degassed under nitrogen for 10 mins
  2. waitleft
  3. customThe reaction mixture was partitioned between ethyl acetate/water (ca. 40 mL each)
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (ca. 25 mL twice)
  6. dry with materialThe combined organic layer were dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified
  9. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-2ea9e87a3a8b43ca8930b2a8f5dec91b
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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