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

HRID 593591Notes

Reaction equation

HRID 593591 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-f1b0ada6db0e4effa105d82ff3d7a655
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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