Diisopropylethylamine → HCID 57896723, compound

HRID 2421899Notes

Reaction equation

HRID 2421899 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][O:14][C:13]3[N:17]=[CH:18][C:19]([C:21](Cl)=[O:22])=[CH:20][C:12]2=3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.O[NH:25][C:26](=[NH:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28].CCN(C(C)C)C(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][O:14][C:13]3[N:17]=[CH:18][C:19]([C:21]4[O:22][N:32]=[C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:25]=4)=[CH:20][C:12]2=3)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 86634653HCID 86634653, compoundHCID 178472862HCID 178472862, compound

Product 1

HCID 57896723HCID 57896723, compoundYield 49.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 1-(4-fluorophenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride (200 mg, 0.561 mmol) in DCM (5 mL) and water (1 mL) was added ethyl 2-(hydroxyamino)-2-iminoacetate (143.5 mg, 1.086 mmol) and DIPEA (230 μL, 1.317 mmol) to give a pink suspension. The reaction was stirred at 40° C. for 1.5 hours. LCMS analysis of the reaction mixture indicated complete consumption of starting material. The reaction mixture was extracted with DCM (2×10 mL) dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was dissolved in THF (6 mL) and treated with TBAF (0.561 mL, 0.561 mmol). The resulting yellow solution was stirred overnight. LCMS analysis of the reaction indicated consumption of the intermediate. The solvent was removed under reduced pressure. The resulting paste was purified by flash column chromatography using a gradient elution of hexanes with 30-100% EtOAc. Ethyl 5-(1-(4-fluorophenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-1,2,4-oxadiazole-3-carboxylate (120 mg, 0.276 mmol, 49.2%) was isolated as an off-white solid. LCMS (+ESI) m/z=435.0 [M+H]+.

Workup

  1. customto give a pink suspension
  2. customconsumption of starting material
  3. extractionThe reaction mixture was extracted with DCM (2×10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting solid was dissolved in THF (6 mL)
  7. stirringThe resulting yellow solution was stirred overnight
  8. customconsumption of the intermediate
  9. customThe solvent was removed under reduced pressure
  10. customThe resulting paste was purified by flash column chromatography
  11. washa gradient elution of hexanes with 30-100% EtOAc

Sources & evidence

ORD record
ord-e1d7899e75984367806da0018c4baf1c
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

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