Pyridine → 3,5-Dichloro-4-(7-fluorothiazolo[5,4-c]pyridin-2-yl)-benzonitrile

HRID 2366277Notes

Reaction equation

HRID 2366277 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[C:11]([F:12])=[CH:10][N:9]=[CH:8][C:7]=1F.NC(N)=[S:24].N1C=CC=CC=1.CCN(CC)CC>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[CH:8]=[N:9][CH:10]=[C:11]([F:12])[C:6]=2[N:5]=1)[C:19]#[N:20]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2723790ThioureaHCID 867233192,6-Dichloro-4-cyano-N-(3,5-difluoropyridin-4-yl)-benzimidoyl chloride

Product 1

HCID 668015813,5-Dichloro-4-(7-fluorothiazolo[5,4-c]pyridin-2-yl)-benzonitrileYield 30%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A stirred suspension of 2,6-dichloro-4-cyano-N-(3,5-difluoropyridin-4-yl)-benzimidoyl chloride (1.5 g, 4.33 mmol), thiourea (1.32 g, 17.34 mmol) and pyridine (1.19 mL, 14.72 mmol) in isopropanol (13 mL) under a nitrogen atmosphere was heated at 90° C. for 4 hours. After cooling to 60° C., Et3N (3.62 mL, 25.98 mmol) was added and heating at 85° C. was continued for 18 hours, then at 90° C. for a further 18 hours. After cooling to room temperature, the volatiles were removed under reduced pressure and the resultant residue was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×2) and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-90% EtOAc in cyclohexane to afford the title compound as a yellow solid (417 mg, 30%). LCMS (Method D): RT=3.53 min, m/z: 324 [M+H+].

Workup

  1. temperatureAfter cooling to 60° C.
  2. temperatureheating at 85° C.
  3. waitat 90° C. for a further 18 hours
  4. temperatureAfter cooling to room temperature
  5. customthe volatiles were removed under reduced pressure
  6. customthe resultant residue was partitioned between EtOAc and water
  7. extractionThe aqueous phase was extracted with EtOAc (×2)
  8. dry with materialthe combined organic layers were dried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-90% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-ebd2a1f90bf447f88eaf5a63e2e65cc4
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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