Piperidine → (1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)(piperidin-1-yl)methanone

HRID 2421891Notes

Reaction equation

HRID 2421891 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.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[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]([N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:21])=[CH:19][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 8082PiperidineHCID 578966591-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride

Product 1

HCID 44242653(1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)(piperidin-1-yl)methanoneYield 68.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a biphasic mixture of 1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride (40 mg, 0.118 mmol) in DCM (1.5 mL) and saturated aqueous NaHCO3 (1.5 mL) was added piperidine (25 μL, 0.253 mmol). The reaction was stirred at room temperature for 16 hours. TLC analysis of the reaction mixture indicated consumption of starting material. The biphasic mixture was extracted with DCM (1.5 mL) (3×2 mL). The combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was purified by flash column chromatography using a gradient elution of hexanes with 10-90% EtOAc to provide (1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)(piperidin-1-yl)methanone (32.5 mg, 0.081 mmol, 68.9% yield) as a white solid. LCMS (+ESI) m/z=388.1 [M+H]+; 1H-NMR (CDCl3) δ 8.25. (d, 1H), 8.14 (d, 1H), 7.66 (m, 2H), 7.61 (tt, 1H), 7.49 (m, 2H), 3.93 (m, 2H), 3.85 (m, 2H), 3.69 (br s, 2H), 3.45 (br s, 2H), 1.75-1.55 (m, 6H).

Workup

  1. customconsumption of starting material
  2. extractionThe biphasic mixture was extracted with DCM (1.5 mL) (3×2 mL)
  3. dry with materialThe combined organics were dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting solid was purified by flash column chromatography
  6. washa gradient elution of hexanes with 10-90% EtOAc

Sources & evidence

ORD record
ord-334e749d4983447c9b9a16bb7ea40551
Source dataset
uspto-grants-2011_06
Patent number
US07960377B2

Reaction notes

Loading…