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

HRID 2421897Notes

Reaction equation

HRID 2421897 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.O[NH:24][C:25](=[NH:28])[CH2:26][CH3:27].CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>[CH2:26]([C:25]1[N:28]=[C:20]([C:18]2[CH:17]=[N:16][C:12]3[O:13][CH2:14][CH2:15][N:10]([S:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)(=[O:9])=[O:8])[C:11]=3[CH:19]=2)[O:21][N:24]=1)[CH3:27]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 578966591-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chlorideHCID 178458070HCID 178458070, compound

Product 1

HCID 442428007-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazineYield 64.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 2724141Tetrabutylammonium FluorideSolvent

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 (2 mL) was added N-hydroxypropionimidamide (20.81 mg, 0.236 mmol) and DIPEA (50 μL, 0.286 mmol). The reaction was stirred at room temperature for 16 hours. LCMS analysis of the reaction mixture indicated consumption of starting material. The reaction mixture was treated with saturated aqueous NaHCO3 (10 mL) and extracted with EtOAc (3×10 mL). The combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was diluted with THF (5 mL) and TBAF in THF (118 μL, 0.118 mmol) was added. The reaction was then stirred overnight. The reaction mixture was concentrated in vacuo and the resulting paste was purified by flash column chromatography using a gradient elution of hexanes with 30-100% EtOAc to provide 7-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (29.7 mg, 0.076 mmol, 64.2% yield) as a white solid. LCMS (+ESI) m/z=373.0 [M+H]+; 1H-NMR (CDCl3) δ 8.87 (d, 1H), 8.77 (d, 1H), 7.71 (m, 2H), 7.63 (tt, 1H) 7.51 (m, 2H), 4.01 (m, 2H), 3.92 (m, 2H), 2.84 (q, 2H), 1.39 (t, 3H).

Workup

  1. customconsumption of starting material
  2. additionThe reaction mixture was treated with saturated aqueous NaHCO3 (10 mL)
  3. extractionextracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organics were dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. additionwas added
  7. stirringThe reaction was then stirred overnight
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. customthe resulting paste was purified by flash column chromatography
  10. washa gradient elution of hexanes with 30-100% EtOAc

Sources & evidence

ORD record
ord-0e6e740a9e5543da87ce3b21c85fde6a
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

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