Pyridine → HCID 10409873, compound

HRID 915506Notes

Reaction equation

HRID 915506 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:9]2[CH:10]=[C:11]([O:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH2:14])=[CH:13][C:8]=2[O:7][C:6]=1[C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:4].N1C=CC=CC=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34].NC1C=CC=CC=1>ClCCl.O>[CH3:1][NH:2][C:3]([C:5]1[C:9]2[CH:10]=[C:11]([O:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH:14][S:33]([CH3:32])(=[O:35])=[O:34])=[CH:13][C:8]=2[O:7][C:6]=1[C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)=[O:4]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6115AnilineHCID 31297Methanesulfonyl chlorideHCID 10450038HCID 10450038, compound

Product 1

HCID 10409873HCID 10409873, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

6-Amino-2-(4-fluoro-phenyl)-5-isopropoxy-benzofuran-3-carboxylic acid methylamide, prepared according to Example 16 (100 mg, 292 μmol) was dissolved in dry dichloromethane (3 mL) under an argon atmosphere. The reaction was cooled down to 0° C. with an ice bath. Pyridine (16.83 μL, 321 μmol) and methanesulfonyl chloride (22.61 μL, 292 μmol) were mixed together under argon, and then added dropwise to the first aniline solution. The reaction mixture was allowed to warm to room temperature for 1 hour. The reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were washed with a 1N HCl solution, water, a saturated aqueous bicarbonate solution and brine and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 20 to 50% ethyl acetate in hexanes gradient) to provide 68 mg (56%) of the product.

Workup

  1. temperatureto warm to room temperature for 1 hour
  2. extractionextracted with dichloromethane (3×10 mL)
  3. washThe combined organic layers were washed with a 1N HCl solution, water
  4. concentrationa saturated aqueous bicarbonate solution and brine and concentrated in vacuo
  5. customThe crude product was purified by column chromatography (silica gel, 20 to 50% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-45837477e3ab4c11bd4f4c1f69d249b2
Source dataset
uspto-grants-2007_09
Patent number
US07265152B2

Reaction notes

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