Triethylamine → ethanesulfonic acid [5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

HRID 1630933Notes

Reaction equation

HRID 1630933 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH3:20])[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([Cl:19])[CH:11]=3)[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.[CH2:28]([S:30](Cl)(=[O:32])=[O:31])[CH3:29]>C(Cl)Cl>[Cl:19][C:12]1[CH:11]=[C:10]2[C:15]([C:16]([C:17]#[N:18])=[C:8]([C:4]3[CH:3]=[C:2]([NH:1][S:30]([CH2:28][CH3:29])(=[O:32])=[O:31])[CH:7]=[N:6][CH:5]=3)[N:9]2[CH3:20])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 582156042-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile

Product 1

HCID 58215794ethanesulfonic acid [5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile (Example 211, 85 mg, 0.3 mmol) in DCM (15 mL) is added triethylamine (122 mg, 1.2 mmol) and ethanesulfonyl chloride (77 mg, 0.6 mmol) and the reaction mixture is stirred overnight. The solvent is removed and the residue is redissolved in methanol (15 mL). Aqueous 1M NaOH (1 mL) is added and the reaction mixture is stirred overnight. The solvent is removed in vacuo and the residue is purified by silica gel flash chromatography (methanol in dichloromethane gradient) to give ethanesulfonic acid [5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (t, J=7.3 Hz, 3H), 3.23-3.33 (m, 2H), 3.79 (s, 3H), 7.36 (dd, J=8.6, 1.8 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.90 (t, J=2.3 Hz, 1H), 7.95 (d, J=1.5 Hz, 1H), 8.61 (d, J=2.3 Hz, 2H), 10.43 (s, 1H). HRMS (ESI) m/z 375.0692 [(M+H)+ Calcd for C17H16ClN4O2S: 375.0682].

Workup

  1. customThe solvent is removed
  2. dissolutionthe residue is redissolved in methanol (15 mL)
  3. additionAqueous 1M NaOH (1 mL) is added
  4. stirringthe reaction mixture is stirred overnight
  5. customThe solvent is removed in vacuo
  6. customthe residue is purified by silica gel flash chromatography (methanol in dichloromethane gradient)

Sources & evidence

ORD record
ord-6fe5dd8d085f449ba8457c41d89d7954
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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