1,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene) → HCID 178504828, compound

HRID 526160Notes

Reaction equation

HRID 526160 reaction equation
C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.[Cl:26][C:27]1[N:32]=[CH:31][C:30]([NH:33][CH:34]=[C:35]([S:41]([CH3:44])(=[O:43])=[O:42])[C:36]([O:38]CC)=O)=[CH:29][CH:28]=1>>[Cl:26][C:27]1[N:32]=[C:31]2[C:30](=[CH:29][CH:28]=1)[N:33]=[CH:34][C:35]([S:41]([CH3:44])(=[O:42])=[O:43])=[C:36]2[OH:38]

Participants

3

Reactant 2

HCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)HCID 131733063Ethyl 3-(6-chloropyridin-3-ylamino)-2-(methylsulfonyl)acrylate

Product 1

HCID 178504828HCID 178504828, compound

Procedure

To a flask containing Dowtherm™ A (500 mL) at 250° C. was added ethyl 3-(6-chloropyridin-3-ylamino)-2-(methylsulfonyl)acrylate (8.2 g, 30 mmol) portion wise over 3 to 5 min and the reaction mixture was stirred for an additional 30 to 45 min. The reaction mixture was removed from the heat source, cooled to room temperature and diluted with hexanes to facilitate precipitation. The solids were collected by filtration, filtered, washed with hexanes and dried under vacuum to afford the intermediate 6-chloro-3-(methylsulfonyl)-1,5-naphthyridin-4-ol which was stirred with heat at 70° C. in neat phosphorus oxychloride (31 mL) with catalytic N,N-dimethylformamide for 4 h. The reaction was cooled and poured slowly into a vigorously stirring mixture of ice-cold satd. aq. sodium bicarbonate and ethyl acetate. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography (silica, hexanes/ethyl acetate) to provide the desired product (2.7 g, 33% over two steps) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 9.50 (s, 1H), 8.46 (d, J=8.8 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 3.41 (s, 3H); ESI MS m/z 278 [M+H]+.

Workup

  1. customThe reaction mixture was removed from the heat source
  2. additiondiluted with hexanes
  3. customprecipitation
  4. filtrationThe solids were collected by filtration
  5. filtrationfiltered
  6. washwashed with hexanes
  7. customdried under vacuum

Sources & evidence

ORD record
ord-da4eb009d8614d84a0acf29a55e0cee7
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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