p-Toluenesulphonyl cyanide → 2-Chloro-6-fluoroimidazo[1,2-A]pyridine-3-carbonitrile

HRID 705075Notes

Reaction equation

HRID 705075 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([F:10])=[CH:6][N:5]2[C:11]=1I.C([Li])CCC.C1(C)C=CC(S([C:27]#[N:28])(=O)=O)=CC=1>O1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([F:10])=[CH:6][N:5]2[C:11]=1[C:27]#[N:28]

Participants

5

Reactant 3

HCID 87946p-Toluenesulphonyl cyanideHCID 717433442-Chloro-6-fluoro-3-iodoimidazo[1,2-A]pyridineHCID 178418339Butyllithium

Product 1

HCID 717433462-Chloro-6-fluoroimidazo[1,2-A]pyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled −78° C. solution of the title compound from Example 3 Step A (0.30 g, 1.01 mmol) in tetrahydrofuran (5.06 ml) was added a solution of n-butyllithium in hexanes (1.6 M, 0.696 ml, 1.11 mmol). After 5 minutes, p-toluenesulfonyl cyanide (0.238 g, 1.32 mmol) was added, and the resulting mixture was allowed to slowly warm to room temperature overnight. The resulting mixture was concentrated under reduced pressure and purified by flash chromatography on silica gel (10-50% ethyl acetate in hexanes) to afford the title compound: LCMS m/z 195.88 [M+H]+, 197.86 [M+2+H]+; 1H NMR (500 MHz, CDCl3) δ 8.25 (d, J=2.4 Hz, 1H), 7.69 (dd, J=9.6, 4.8 Hz, 1H), 7.46-7.42 (m, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. custompurified by flash chromatography on silica gel (10-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fce6c14083854af4b7c41a00488cfa21
Source dataset
uspto-grants-2015_11
Patent number
US09173873B2

Reaction notes

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