Pyridine → HCID 66801290, compound

HRID 2366259Notes

Reaction equation

HRID 2366259 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[C:11]([F:12])=[CH:10][N:9]=[CH:8][C:7]=1F.NC(N)=[S:22].N1C=CC=CC=1.CCN(CC)CC>C(O)(C)C>[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:3]=1[C:4]1[S:22][C:7]2[CH:8]=[N:9][CH:10]=[C:11]([F:12])[C:6]=2[N:5]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2723790ThioureaHCID 86669006HCID 86669006, compound

Product 1

HCID 66801290HCID 66801290, compoundYield 41.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

A stirred suspension of 2-chloro-N-(3,5-difluoropyridin-4-yl)-6-fluorobenzimidoyl chloride (12.0 g, 39.4 mmol), thiourea (9.0 g, 118 mmol) and pyridine (12.7 mL, 198 mmol) in isopropanol (200 mL) was heated at 150° C. for 3.5 hours. After stirring for one additional hour, the resulting precipitate was collected by filtration. The filtrate was treated with Et3N (27 mL, 0.197 mol) and heating was continued at 150° C. for 18 hours. After cooling to room temperature, the volatiles were removed under reduced pressure and the resultant residue was partitioned between EtOAc (300 mL) and water (500 mL). The aqueous phase was extracted with EtOAc (2×300 mL) and the combined organic layers were dried and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-100% Et2O in petroleum ether and then triturated with a mixture 3:1 diethyl ether:pentane (25 mL) to afford the title compound as a cream coloured solid (4.6 g, 41%). LCMS (Method F): RT=3.39 min, m/z: 283 [M+H+].

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. temperatureheating
  3. temperatureAfter cooling to room temperature
  4. customthe volatiles were removed under reduced pressure
  5. customthe resultant residue was partitioned between EtOAc (300 mL) and water (500 mL)
  6. extractionThe aqueous phase was extracted with EtOAc (2×300 mL)
  7. customthe combined organic layers were dried
  8. concentrationconcentrated under reduced pressure
  9. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-100% Et2O in petroleum ether
  10. customtriturated with a mixture 3:1 diethyl ether

Sources & evidence

ORD record
ord-ac2224aad63e44d7b296fbfd76f1ef7b
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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