Methyl iodide → N-methyl-1H-pyrrolo[2,3-b]pyridin-5-amine

HRID 1064258Notes

Reaction equation

HRID 1064258 reaction equation
C([Si](C(C)C)(C(C)C)[N:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH2:14])[CH:13]=[C:8]2[CH:7]=[CH:6]1)(C)C.[CH2:21](N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(OC(=O)N)(C)(C)C.[H-].[Na+].CI>ClCCl.CN(C=O)C>[CH3:21][NH:14][C:12]1[CH:13]=[C:8]2[CH:7]=[CH:6][NH:5][C:9]2=[N:10][CH:11]=1

Participants

9

Reactant 6

HCID 6328Methyl iodideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 77922tert-Butyl carbamateHCID 90495Di-tert-butyl dicarbonateHCID 222736141-[Tri(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridin-5-amine

Product 1

HCID 22273610N-methyl-1H-pyrrolo[2,3-b]pyridin-5-amineYield 33%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-Triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-ylamine (375 mg, 1.3 mmol) and triethylamine (271 μL, 1.95 mmol) in dichloromethane (10 mL) was treated with di-tert-butyl dicarbonate (340 mg, 1.5 mmol) and the mixture was stirred at RT for 2.5 h., quenched with saturated ammonium chloride (20 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4.), filtered and concentrated. The residue was purified by preparative HPLC. B. 1-Triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-carbamic acid tert-butyl ester (250 mg, 0.6 mmol) was then treated with sodium hydride (24 mg, 60% oil, 0.6 mmol) and methyl iodide (48 mL, 0.77 mmol) in DMF (2.0 mL). The mixture was stirred at RT for 16 h, quenched with saturated ammonium chloride (20 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4.), filtered and concentrated. The residue, which was used with no further purification, was then treated with TFA (1.0 mL) in dichloromethane (4.0 mL) and the mixture was stirred at RT for 10 h, concentrated and purified by preparative HPLC to afford methyl(1H-pyrrolo[2,3-b]pyridin-5-yl)-amine (31 mg, 33%). m/z 148 (M+H)+.

Workup

  1. customquenched with saturated ammonium chloride (20 mL)
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried (MgSO4.)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC
  8. stirringThe mixture was stirred at RT for 16 h
  9. customquenched with saturated ammonium chloride (20 mL)
  10. extractionextracted with ethyl acetate (3×25 mL)
  11. washThe combined organic layers were washed with brine (50 mL)
  12. dry with materialdried (MgSO4.)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue, which was used with no further purification
  16. additionwas then treated with TFA (1.0 mL) in dichloromethane (4.0 mL)
  17. stirringthe mixture was stirred at RT for 10 h
  18. concentrationconcentrated
  19. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-a23d7d75c23449ae87031bae6b72a436
Source dataset
uspto-grants-2005_11
Patent number
US06969717B2

Reaction notes

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