Pyridine → 3-Chloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluorobenzonitrile

HRID 2366228Notes

Reaction equation

HRID 2366228 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([F:21])[C:3]=1[C:4](Cl)=[N:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([Cl:12])[C:7]=1F.NC(N)=[S:24].N1C=CC=CC=1.C(N(CC)CC)C>C(O)(C)C>[Cl:1][C:2]1[CH:18]=[C:17]([CH:16]=[C:15]([F:21])[C:3]=1[C:4]1[S:24][C:7]2[C:8]([Cl:12])=[N:9][CH:10]=[CH:11][C:6]=2[N:5]=1)[C:19]#[N:20]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2723790ThioureaHCID 867233132-Chloro-N-(2-chloro-3-fluoropyridin-4-yl)-4-cyano-6-fluorobenzimidoyl chloride

Product 1

HCID 867233143-Chloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluorobenzonitrileYield 53.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 2-chloro-N-(2-chloro-3-fluoropyridin-4-yl)-4-cyano-6-fluorobenzimidoyl chloride (0.713 g, 2.05 mmol), thiourea (0.623 g, 8.2 mmol) and pyridine (538 μL, 6.66 mmol) in isopropanol (7 mL) was heated under reflux for 3 hours. The reaction mixture was allowed to cool to ambient temperature before adding triethylamine (1.7 mL, 12.3 mmol). The resulting mixture was heated under reflux for a further 3 hours and allowed to cool. The mixture was concentrated under reduced pressure and the residue was partitioned between DCM and water. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography (0-10% EtOAc in pentane) to give the desired compound as an off-white solid (0.356 g, 53% yield). 1H NMR (300 MHz, CDCl3): δ 8.55 (d, J=5.6 Hz, 1H), 8.01 (d, J=5.6 Hz, 1H), 7.72 (t, J=1.4 Hz, 1H), 7.52 (dd, J=8.3, 1.5 Hz, 1H). LCMS (Method D): RT=3.86 min, m/z: 324 [M+H+].

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 hours
  3. temperatureThe resulting mixture was heated
  4. temperatureunder reflux for a further 3 hours
  5. temperatureto cool
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customthe residue was partitioned between DCM and water
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe crude residue was purified by silica gel flash chromatography (0-10% EtOAc in pentane)

Sources & evidence

ORD record
ord-657541e915e54b6793a4ab1220cb46c9
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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