Toluene → N-[5-(6-Chloro-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide

HRID 1630927Notes

Reaction equation

HRID 1630927 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:18]=O)[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH2:20]([S:22]([NH2:25])(=[O:24])=[O:23])[CH3:21].C1(C)C=CC=CC=1.[BH4-].[Na+]>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:12]3[CH:17]=[C:16]([CH2:18][NH:25][S:22]([CH2:20][CH3:21])(=[O:24])=[O:23])[CH:15]=[N:14][CH:13]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 73702EthanesulfonamideHCID 4311764Sodium borohydrideHCID 454897085-(6-chloro-1-methyl-1H-indol-2-yl)nicotinaldehyde

Product 1

HCID 58215567N-[5-(6-Chloro-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

A flask is charged with 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole (Example 126a, 1.2 g, 4.43 mmol), ethanesulfonamide (0.726 g, 6.65 mmol), titanium(IV) isopropoxide (2.60 mL, 8.87 mmol) and toluene (50 mL). The reaction mixture is refluxed overnight and then concentrated to dryness. The crude material (1.60 g) is dissolved in MeOH (24 mL) and DCM (24 mL), and sodium borohydride (0.335 g, 8.87 mmol) is added. The reaction mixture is stirred at room temperature for 2 h, then concentrated in vacuo. The residue is taken up in DCM and washed with water twice. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. Purification is achieved by silica gel flash chromatography to give N-[5-(6-Chloro-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide. 1H NMR (400 MHz, MeOD) δ ppm 1.38 (t, J=7.3 Hz, 3H), 3.14 (q, J=7.3 Hz, 2H), 3.80 (s, 3H), 4.43 (s, 2H), 6.72 (s, 1H), 7.12 (dd, J=8.5, 1.9 Hz, 1H), 7.54 (d, J=1.8 Hz, 1H), 7.59 (d, J=8.6 Hz, 1H), 8.10 (t, J=2.1 Hz, 1H), 8.63 (d, J=2.0 Hz, 1H), 8.71 (d, J=2.0 Hz, 1H). HRMS (ESI) m/z 364.0869 [(M+H)+ Calcd for C17H19ClN3O2S: 364.0887].

Workup

  1. temperatureThe reaction mixture is refluxed overnight
  2. concentrationconcentrated to dryness
  3. dissolutionThe crude material (1.60 g) is dissolved in MeOH (24 mL)
  4. concentrationconcentrated in vacuo
  5. washwashed with water twice
  6. dry with materialThe organic layer is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification

Sources & evidence

ORD record
ord-bdf9b67579d44272aeccf8e52c1ca581
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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