Selectfluor → 3-Fluoro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 549018Notes

Reaction equation

HRID 549018 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[NH:21][C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH:14]=1.C[Mg]Br.[F:25][B-](F)(F)F.F[B-](F)(F)F.ClC[N+]12CC[N+](F)(CC1)CC2>O1CCCC1>[F:25][C:14]1[C:15]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[NH:21][C:13]=1[C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:8]([CH3:12])[CH:7]=1

Participants

5

Reactant 3

HCID 2724933SelectfluorHCID 224772272-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridineHCID 178418573HCID 178418573, compound

Product 1

HCID 224772553-Fluoro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridineYield 53.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(5-methoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyridine [0.1 g, Example 17(a)] in dry tetrahydrofuran (4 mL), at 0° C., was treated with methyl magnesium bromide (0.042 mL) and after stirring for a further 20 minutes at 0° C. this mixture was treated with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate) (0.13 g). The reaction mixture was stirred at room temperature for 4 hours, then stood at room temperature overnight, then heated at 40° C. for 4 hours, then heated at 80° C. for 2 hours, then cooled to room temperature and then partitioned between ethyl acetate and water. The aqueous layer was extracted three times with ethyl acetate (25 mL). The combined extracts and ethyl acetate layer from the partitioning were washed with brine, then dried over magnesium sulfate and then evaporated. The residue was triturated with ethyl acetate to give the title compound (0.057 g) as a white solid, m.p. 248-250° C. 1H NMR [(CD3)2SO]: δ 12.20 (1H, s); 8.24 (1H, m); 7.81 (1H, s); 7.79 (1H, d, J=9.6 Hz); 7.46 (1H, d, J=9.6 Hz); 7.27 (1H, s); 7.18 (1H, dd, J=13.1, 6.0 Hz); 6.90 (1H, d, J=9.6 Hz); 3.88 (3H, s); 3.80 (3H, s).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 hours
  2. waitstood at room temperature overnight
  3. temperatureheated at 40° C. for 4 hours
  4. temperatureheated at 80° C. for 2 hours
  5. temperaturecooled to room temperature
  6. custompartitioned between ethyl acetate and water
  7. extractionThe aqueous layer was extracted three times with ethyl acetate (25 mL)
  8. washThe combined extracts and ethyl acetate layer from the partitioning were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-a5f042154be94e14807719e24024b9c3
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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