Pyridine → 4-Chloro-2-(2-chloro-6-fluorophenyl)-thiazolo[5,4-c]pyridine

HRID 2366197Notes

Reaction equation

HRID 2366197 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[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:22].N1C=CC=CC=1.C(N(CC)CC)C>C(O)(C)C>[Cl:12][C:8]1[C:7]2[S:22][C:4]([C:3]3[C:15]([F:19])=[CH:16][CH:17]=[CH:18][C:2]=3[Cl:1])=[N:5][C:6]=2[CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2723790ThioureaHCID 86723304HCID 86723304, compound

Product 1

HCID 867233054-Chloro-2-(2-chloro-6-fluorophenyl)-thiazolo[5,4-c]pyridineYield 86.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 2-chloro-N-(2-chloro-3-fluoro-pyridin-4-yl)-6-fluorobenzimidoyl chloride (80 mg, 0.25 mmol), thiourea (76 mg, 1.0 mmol) and pyridine (82 μL, 1.0 mmol) in anhydrous isopropanol (1.5 mL) was heated under reflux, under nitrogen, for 3.5 hours. The reaction mixture was allowed to cool to ambient temperature and then triethylamine (1 mL) was added. The resultant mixture was heated under reflux for a further 1 hour then cooled to ambient temperature. The mixture was concentrated to dryness under reduced pressure and the residue was triturated with DCM, filtered and left to air dry. The crude product was purified by silica gel flash chromatography (0-10% EtOAc in cyclohexane) to give the desired compound as a white solid (65 mg, 86% yield). 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J=5.6 Hz, 1H), 7.99 (d, J=5.6 Hz, 1H), 7.50 (td, J=8.3, 5.8 Hz, 1H), 7.41 (dt, J=8.2, 1.1 Hz, 1H), 7.21 (ddd, J=9.0, 8.4, 1.1 Hz, 1H). LCMS (Method C): RT=3.90 min, m/z: 299 [M+H+].

Workup

  1. temperaturewas heated
  2. temperatureunder reflux, under nitrogen, for 3.5 hours
  3. temperatureunder reflux for a further 1 hour
  4. temperaturethen cooled to ambient temperature
  5. concentrationThe mixture was concentrated to dryness under reduced pressure
  6. customthe residue was triturated with DCM
  7. filtrationfiltered
  8. waitleft to air
  9. customdry
  10. customThe crude product was purified by silica gel flash chromatography (0-10% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-a0ede95bb9764b7c9763971172b45629
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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