Dimethylformamide → 5-chloro-7-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

HRID 1630861Notes

Reaction equation

HRID 1630861 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH3:12])[C:6]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[CH:5]2.ClS([N:23]=[C:24]=O)(=O)=O.CN(C=O)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH3:12])[C:6]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[C:5]2[C:24]#[N:23]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 582155765-chloro-7-fluoro-1-methyl-2-pyridin-3-yl-1H-indole

Product 1

HCID 582156505-chloro-7-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-7-fluoro-1-methyl-2-pyridin-3-yl-1H-indole (130 mg, 0.50 mmol) in dichloromethane (10 mL) at ambient temperature is added chlorosulfonyl isocyanate (282 mg, 2.0 mmol) and the mixture is stirred for 11 h, whereupon anhydrous DMF (1 mL) is added. After 1 h, the mixture is concentrated and the residue is purified by HPLC using an Xbridge C18 with a gradient of acetonitrile in 0.1% NH4OH to afford 5-chloro-7-fluoro-1-methyl-2-pyridin-3-yl-1H-indole-3-carbonitrile as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.89 (d, J=1.8 Hz, 3H), 7.46 (dd, J=12.4, 1.8 Hz, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.71 (dd, J=7.5, 4.4 Hz, 1H), 8.16 (dt, J=8.1, 2.0, 1.8 Hz, 1H), 8.83 (dd, J=4.9, 1.6 Hz, 1H), 8.89 (d, J=1.5 Hz, 1H). HRMS (ESI) m/z 286.0558 [(M+H)+ Calcd for C15H10ClFN3: 286.0547].

Workup

  1. additionis added
  2. concentrationthe mixture is concentrated
  3. customthe residue is purified by HPLC

Sources & evidence

ORD record
ord-cae413248e174a26a205f63360f2925a
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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