Pyridine → 3,5-Dichloro-4-(4-chloro-thiazolo[5,4-c]pyridine-2-yl)-benzonitrile

HRID 2366211Notes

Reaction equation

HRID 2366211 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([Cl: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]([Cl: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 86668994HCID 86668994, compound

Product 1

HCID 866689933,5-Dichloro-4-(4-chloro-thiazolo[5,4-c]pyridine-2-yl)-benzonitrileYield 65%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 2,6-dichloro-N-(2-chloro-3-fluoro-pyridin-4-yl)-4-cyano-benzimidoyl chloride (454 mg, 1.25 mmol), thiourea (380 mg, 5.0 mmol) and pyridine (325 μL, 4.0 mmol) in anhydrous isopropanol (4 mL) was heated under reflux, under nitrogen, for 16 hours. Triethylamine (1.05 mL, 7.5 mmol) was added and the resultant mixture was heated under reflux for a further 6.5 hours. The mixture was cooled to ambient temperature and concentrated to dryness under reduced pressure. The residue was partitioned between DCM (15 mL) and water (15 mL). The aqueous phase was extracted with DCM (2×10 mL) and the combined organic extract was dried over MgSO4 and concentrated to dryness under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 0-20% EtOAc in DCM. The resultant solid was triturated with cyclohexane and dried under reduced pressure to give the desired compound as a white solid (275 mg, 65% yield). 1H NMR (400 MHz, CDCl3): δ 8.55 (d, J=5.6 Hz, 1H), 8.00 (d, J=5.6 Hz, 1H), 7.79 (s, 2H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux, under nitrogen, for 16 hours
  3. temperatureunder reflux for a further 6.5 hours
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe residue was partitioned between DCM (15 mL) and water (15 mL)
  6. extractionThe aqueous phase was extracted with DCM (2×10 mL)
  7. extractionthe combined organic extract
  8. dry with materialwas dried over MgSO4
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue was purified by silica gel flash chromatography
  11. washeluting with 0-20% EtOAc in DCM
  12. customThe resultant solid was triturated with cyclohexane
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-b11a78f426224d25a681a35c6aa4bf44
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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