Sulfuryl chloride → 3-[(4-Chlorophenyl)sulfanyl]-2,5-dimethyl-1H-indole-4-carbonitrile

HRID 2240551Notes

Reaction equation

HRID 2240551 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]([CH3:12])=O)=[CH:4][CH:3]=1.S(Cl)(Cl)(=O)=O.C[N:19](C)[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][C:28]=2N(C)C)[CH:23]=CC=1.[NH2:34]C1C=CC(Cl)=C(C=1)C#N>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:28]3[C:29]([C:20]#[N:19])=[C:24]([CH3:23])[CH:25]=[CH:26][C:27]=3[NH:34][C:10]=2[CH3:12])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24648Sulfuryl chlorideHCID 88675Proton spongeHCID 3217461-[(4-Chlorophenyl)sulfanyl]propan-2-oneHCID 109972345-Amino-2-chlorobenzonitrile

Product 1

HCID 210778313-[(4-Chlorophenyl)sulfanyl]-2,5-dimethyl-1H-indole-4-carbonitrileYield 12.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A stirred solution of 1-[(4-chlorophenyl)thio]-acetone (6.14 g) in dry dichloromethane (150 ml) at −78° C. was treated with sulphuryl chloride (2.25 ml). After 30 min a prepared solution of N,N,N′,N′-tetramethyl-1,8-naphthalenediamine (6.01 g) and 5-amino-2-chloro-benzonitrile (3.89 g) in dry dicholoromethane (80 ml) was added dropwise over 30 min. The mixture was stirred for a further 2 h, after which triethylamine (4.26 ml) was added and the reaction allowed to reach room temperature. The reaction mixture was diluted with dichloromethane (200 ml), washed with water, 1N HCl and brine. The organic phase was dried (MgSO4), evaporated in vacuo, and the residue purified by flash column chromatography eluting with isohexane and ethyl acetate (1:1) to give the sub-title compound (1 g), and the regioisomer (600 mg) used in example 6 below.

Workup

  1. customto reach room temperature
  2. washwashed with water, 1N HCl and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated in vacuo
  5. customthe residue purified by flash column chromatography
  6. washeluting with isohexane and ethyl acetate (1:1)

Sources & evidence

ORD record
ord-54ed0134b48c427a9a2e6034bc8f55ea
Source dataset
uspto-grants-2010_05
Patent number
US07723373B2

Reaction notes

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