Pyridine → Methyl 5-amino-1H-indole-3-carboxylate

HRID 507355Notes

Reaction equation

HRID 507355 reaction equation
ClC1C(C)=C(S(Cl)(=O)=O)C=CC=1.N1C=CC=C[CH:14]=1.COC([C:23]1[NH:24][C:25]2[C:30]([CH:31]=1)=[CH:29][C:28]([NH2:32])=[CH:27][CH:26]=2)=O.[C:33]([O-:36])(O)=[O:34].[Na+]>ClCCl>[CH3:14][O:36][C:33]([C:31]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([NH2:32])[CH:29]=2)[NH:24][CH:23]=1)=[O:34]

Participants

6

Reactant 4

HCID 1049PyridineHCID 516892Sodium BicarbonateHCID 5227343-Chloro-2-methylbenzenesulfonyl chlorideHCID 10330149Methyl 5-amino-1H-indole-2-carboxylate

Product 1

HCID 45089221Methyl 5-amino-1H-indole-3-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-chloro-2-methylbenzenesulphonyl chloride (124 mg, 0.552 mmol) in dichloromethane (4 mL) was added pyridine (100 μL, 1.3 mmol) and the mixture was stirred under N2 for 5 min, after which time 5-amino-1H-indole-carboxylic acid methyl ester (100 mg, 0.526 mmol) was added. The resulting mixture was stirred for 1.5 h at room temperature, then saturated NaHCO3 solution (15 mL) was added and the mixture was extracted into ethyl acetate (20 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to give a residue that was purified using flash chromatography to afford a white solid (129 mg, 65%), single spot at Rf 0.84 (ethyl acetate). mp 216.8-219.3° C., [22], HPLC purity 99+% (tR 2.07 min in 10% water-acetonitrile). 1H NMR (d6-DMSO): δ 11.91 (1H, s), 10.32 (1H, s), 8.03 (1H, d, J=3.0 Hz), 7.82 (1H, d, J=7.9 Hz), 7.70-7.67 (2H, m), 7.37-7.31 (2H, m), 6.95 (1H, dd, J=8.6, 2.0 Hz), 3.77 (3H, s), 2.65 (3H, s). LCMS: 377.09. FAB-MS (MH+, C17H15ClN2O4S): calcd 378.0441, found 378.0439.

Workup

  1. stirringThe resulting mixture was stirred for 1.5 h at room temperature
  2. extractionthe mixture was extracted into ethyl acetate (20 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a residue that
  8. customwas purified

Sources & evidence

ORD record
ord-65b06e9f616b4ceaaa0736db5df97c6f
Source dataset
uspto-grants-2010_08
Patent number
US07786152B2

Reaction notes

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