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

HRID 331004Notes

Reaction equation

HRID 331004 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH3:14])[CH:3]=1.[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.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>[CH3:14][N:4]1[C:5]2=[N:6][CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[C:10]2[C:2]([C:22]2[CH:23]=[C:24]3[C:19]([CH2:18][CH2:17][N:16]3[CH3:15])=[CH:20][CH:21]=2)=[CH:3]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 709799671-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolineHCID 710900843-Iodo-1-methyl-4-nitro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 710903071-methyl-3-(1-methylindolin-6-yl)-4-nitro-1H-pyrrolo[2,3-b]pyridineYield 49.8%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 3-iodo-1-methyl-4-nitro-1H-pyrrolo[2,3-b]pyridine (D17) (6.2 g, 20.46 mmol) in ACN (108 mL) was added 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (7.95 g, 30.7 mmol), bis(triphenylphosphine)palladium(II) chloride (1.436 g, 2.046 mmol) and 2M sodium carbonate aq. solution (108 mL, 217 mmol). The resulting mixture was heated at 65° C. for ca. 1 hour. After being cooled to RT, the reaction mixture was diluted with DCM (150 mL) and water (200 mL). The organic phase was separated and the aqueous phase was further extracted with DCM (80 mL×4). The combined organics were dried and concentrated. The residue was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane to give an impure fraction which was re-purified by chromatography on silica, eluting with a gradient of 0-20% ethyl acetate in DCM to give the title compound (3.14 g). LCMS (A): m/z (M+H)+ 309, C17H16N4O2 requires 308 (acidic).

Workup

  1. temperatureAfter being cooled to RT
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was further extracted with DCM (80 mL×4)
  4. customThe combined organics were dried
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica
  7. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
  8. customto give an impure fraction which
  9. customwas re-purified by chromatography on silica
  10. washeluting with a gradient of 0-20% ethyl acetate in DCM

Sources & evidence

ORD record
ord-a1511065559c4e89aa17e233d2af7315
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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