Dimethylformamide → 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile

HRID 593593Notes

Reaction equation

HRID 593593 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:19])[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1.ClS([N:24]=[C:25]=O)(=O)=O.CN(C=O)C.C([O-])(O)=O.[Na+].C(N(CC)CC)C>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:25]#[N:24])=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:18]=[O:19])[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 516892Sodium BicarbonateHCID 454897085-(6-chloro-1-methyl-1H-indol-2-yl)nicotinaldehyde

Product 1

HCID 582157716-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A flask is charged with 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole (10 g, 36.9 mmol) and acetonitrile (1 L), and chlorosulfonyl isocyanate (15.68 g, 111 mmol) is added at 0° C. The mixture is stirred for 10 min. DMF (18.9 g, 259 mmol) is added at 0° C. The mixture is stirred for 1.5 h. Saturated NaHCO3 (20 mL) and triethylamine (51.5 mL, 369 mmol) are added to the reaction mixture, which is stirred for 10 min. The mixture is concentrated in vacuo to give a residue which is purified by silica gel flash chromatography eluting with a 0 to 5% methanol-DCM gradient to give 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile. MS (ESI) m/z 296.0, 297.8 (M+H)+.

Workup

  1. additionis added at 0° C
  2. stirringThe mixture is stirred for 1.5 h
  3. stirringis stirred for 10 min
  4. concentrationThe mixture is concentrated in vacuo
  5. customto give a residue which
  6. customis purified by silica gel flash chromatography
  7. washeluting with a 0 to 5% methanol-DCM gradient

Sources & evidence

ORD record
ord-f8986ead44bc40528913207fb62f47c6
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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