Hydrochloric Acid → HCID 118022145, compound

HRID 575622Notes

Reaction equation

HRID 575622 reaction equation
[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[F:31])=[C:12]([C:14]2[C:15]([F:22])=[CH:16][C:17](=[O:21])[N:18]([CH3:20])[CH:19]=2)[CH:13]=1.N1C=CC=CC=1.Cl>ClCCl>[F:31][C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[O:23][C:11]1[CH:10]=[CH:9][C:8]([NH:7][S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:13][C:12]=1[C:14]1[C:15]([F:22])=[CH:16][C:17](=[O:21])[N:18]([CH3:20])[CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 11667Ethanesulfonyl chlorideHCID 118021388HCID 118021388, compound

Product 1

HCID 118022145HCID 118022145, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethylsulfonyl chloride (177 mg, 1.4 mmol) was added dropwise to a stirred solution of 5-[5-amino-2-(2,4-difluorophenoxy)phenyl]-4-fluoro-1-methylpyridin-2-one (72 mg, 0.21 mmol) and pyridine (50 mL, 0.63 mmol) in dichloromethane (500 mL) at 0° C. under nitrogen. After the mixture was allowed to warm to rt and stir for 2 h, it was treated with 1N HCl (3 mL) and extracted with dichloromethane (3×10 mL); the combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (4 g ISCO, gradient 0-10% MeOH in dichloromethane) to afford the desired product, N-[4-(2,4-difluorophenoxy)-3-(4-fluoro-1-methyl-6-oxopyridin-3-yl)phenyl]ethanesulfonamide (66 mg, 72%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.18-1.26 (m, 3H), 3.07-3.16 (m, 2H), 3.45 (s, 3H), 6.22-6.33 (m, 1H), 6.82-6.93 (m, 1H), 7.01-7.16 (m, 2H), 7.18-7.28 (m, 2H), 7.38-7.49 (m, 1H), 7.95-8.05 (m, 1H), 9.77-9.87 (s, 1H). LCMS (M+H)+=439.

Workup

  1. extractionextracted with dichloromethane (3×10 mL)
  2. washthe combined organic extracts were washed with saturated bicarbonate solution (aq)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel column chromatography (4 g ISCO, gradient 0-10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-00895b5876c44ca995817b5a6f80c1c7
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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