Benzoylhydrazine → 7-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine

HRID 2421898Notes

Reaction equation

HRID 2421898 reaction equation
[C:1]1([S:7]([N:10]2[CH2:15][CH2:14][O:13][C:12]3[N:16]=[CH:17][C:18]([C:20](Cl)=[O:21])=[CH:19][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23]([NH:31][NH2:32])(=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C(Cl)Cl>[C:24]1([C:23]2[O:21][C:20]([C:18]3[CH:17]=[N:16][C:12]4[O:13][CH2:14][CH2:15][N:10]([S:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)(=[O:9])=[O:8])[C:11]=4[CH:19]=3)=[N:32][N:31]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 11955BenzoylhydrazineHCID 81531DiisopropylethylamineHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 578966591-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride

Product 1

HCID 578968027-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazineYield 8.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride (40 mg, 0.118 mmol; Example 1 Step 1) in DCM (1.5 mL) was added benzohydrazide (32.2 mg, 0.236 mmol) and DIPEA (50 μL, 0.286 mmol). The reaction was stirred at room temperature for 16 hours. TLC analysis of the reaction mixture indicated consumption of starting material. The reaction was quenched with saturated aqueous NaHCO3 (2 mL) and was extracted with DCM (3×2 mL). The combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was dissolved in DMF (3 mL) and treated with Burgess reagent (28.1 mg, 0.118 mmol). The reaction mixture was heated to 180° C. by heating under microwave irradiation for 5 minutes. The mixture was concentrated in vacuo. The resulting paste was purified by flash column chromatography using a gradient elution of hexanes with 10-90% EtOAc. The resulting tan solid was triturated with water (2×10 mL) to provide 7-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (4.6 mg, 10.39 μmol, 8.80% yield) as a white solid. LCMS (+ESI) m/z=421.0 [M+H]+; 1H-NMR (CDCl3) δ 8.90 (d, 1H), 8.84 (d, 1H), 8.17 (m, 2H), 7.74 (m, 2H), 7.65 (tt, 1H), 7.59-7.51 (m, 5H), 4.02 (m, 2H), 3.95 (m, 2H).

Workup

  1. customconsumption of starting material
  2. customThe reaction was quenched with saturated aqueous NaHCO3 (2 mL)
  3. extractionwas extracted with DCM (3×2 mL)
  4. dry with materialThe combined organics were dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting solid was dissolved in DMF (3 mL)
  7. temperatureThe reaction mixture was heated to 180° C.
  8. temperatureby heating under microwave irradiation for 5 minutes
  9. concentrationThe mixture was concentrated in vacuo
  10. customThe resulting paste was purified by flash column chromatography
  11. washa gradient elution of hexanes with 10-90% EtOAc
  12. customThe resulting tan solid was triturated with water (2×10 mL)

Sources & evidence

ORD record
ord-da1b456eeb0748c0b53975d4a0643bb1
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

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