Pyridine → 4-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenyl]-amide

HRID 1660794Notes

Reaction equation

HRID 1660794 reaction equation
[OH:1][NH:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:22][CH2:21][CH2:20][N:19]([S:23]([C:26]4[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=4[O:33][CH3:34])(=[O:25])=[O:24])[C:18]=3[CH:35]=2)=[O:13])=[CH:7][CH:6]=1)=[NH:4].N1C=CC=CC=1.C(C(CCCC)[CH2:45][O:46]C(Cl)=O)C>CN(C)C=O.O>[O:46]=[C:45]1[O:1][N:2]=[C:3]([C:5]2[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]3[CH:15]=[CH:16][C:17]4[O:22][CH2:21][CH2:20][N:19]([S:23]([C:26]5[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=5[O:33][CH3:34])(=[O:24])=[O:25])[C:18]=4[CH:35]=3)=[O:13])=[CH:7][CH:6]=2)[NH:4]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 627832-Ethylhexyl chloroformateHCID 178490722HCID 178490722, compound

Product 1

HCID 1357498264-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenyl]-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-(5-chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [4-(N-hydroxycarbamimidoyl)-phenyl]-amide (97 mg, 0.19 mmol) in dimethylformamide (2.0 mL) was treated with pyridine (0.020 mL, 0.20 mmol) and the mixture was cooled at 0° C. Chloroformic acid 2-ethylhexyl ester (36 mg, 0.19 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min. The mixture was diluted with water and extracted three times with ethyl acetate. The combined organic extracts were dried over sodium sulfate and evaporated. The residue was suspended in xylene (8.0 mL) and refluxed for 2 hours. Upon cooling to room temperature a solid precipitated, which was filtered and dried under high vacuum. 4-(5-Chloro-2-methoxy-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenyl]-amide was obtained as a white solid, 74 mg (73%), MS (ISP): m/e=541.1, 542.7 (M−H).

Workup

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. customevaporated
  4. temperaturerefluxed for 2 hours
  5. temperatureUpon cooling to room temperature a solid
  6. customprecipitated
  7. filtrationwhich was filtered
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-39a4971baa2042939a08052fb71bd0c2
Source dataset
uspto-grants-2011_10
Patent number
US08030308B2

Reaction notes

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