Pyridine → 6-methyl-4H-pyrido[4,3-b][1,4]oxazine-3,5-dione

HRID 518529Notes

Reaction equation

HRID 518529 reaction equation
Cl.[NH2:2][C:3]1[C:4](=[O:11])[N:5]([CH3:10])[CH:6]=[CH:7][C:8]=1[OH:9].Cl[CH2:13][C:14](Cl)=[O:15].N1C=CC=CC=1.OS([O-])(=O)=O.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl.CC(=O)OCC.C(O)(C)C.O>[CH3:10][N:5]1[CH:6]=[CH:7][C:8]2[O:9][CH2:13][C:14](=[O:15])[NH:2][C:3]=2[C:4]1=[O:11]

Participants

10

Reactant 5

HCID 1049PyridineHCID 6577Chloroacetyl chlorideHCID 10796Cesium carbonateHCID 516920Potassium bisulfateHCID 1180221633-amino-4-hydroxy-1-methylpyridin-2(1H)-one hydrochloride

Product 1

HCID 1180216156-methyl-4H-pyrido[4,3-b][1,4]oxazine-3,5-dioneYield 24.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the title compound of Example 237, step 3 (1.6 g, 9.01 mmol, 1.00 Eq) in CH2Cl2 (150 mL) at 0° C. under N2 is added chloroacetyl chloride (0.75 mL, 9 mmol) dropwise. Pyridine (2.2 mL, 37 mmol) is then added, and the mixture was stirred for 5 h at room temperature. Saturated aqueous KHSO4 (100 mL) is added and the aqueous layer was extracted a total of three times with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and then acetone (200 mL) followed by cesium carbonate (14.6 g, 45 mmol) were added directly to the filtrate (250 mL). The mixture was then heated at 50° C. for 2 h. The volume was reduced and water was added. Extractive work up with 3:1 CH2Cl2: isopropanol followed by trituration with 1:2 EA/PE gave the title compound (400 mg, yield: 24.67%) as a yellow solid. 1H NMR: (CDCl3, 400 MHz) δ: 8.17-8.14 (br, 1H), 7.01 (d, J=7.2 Hz, 1H), 6.07 (d, J=7.2 Hz, 1H), 4.69 (s, 1H), 3.59 (s, 3H). LCMS: 181.0 (M+H)+

Workup

  1. extractionthe aqueous layer was extracted a total of three times with CH2Cl2
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. temperatureThe mixture was then heated at 50° C. for 2 h

Sources & evidence

ORD record
ord-a84bfe99e50d47f48301f56b6d1236c8
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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