Triethylamine → 2,4-dioxo-N-(tetrahydro-2H-pyran-2-yloxy)-1,2,3,4-tetrahydroquinazoline-7-carboxamide

HRID 1616123Notes

Reaction equation

HRID 1616123 reaction equation
[O:1]=[C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][C:6]([C:13]([OH:15])=O)=[CH:7][CH:8]=2)[NH:3]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.FC(N(C)C)=[N+](C)C.[O:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH:39]1[O:44][NH2:45]>O.CN(C=O)C>[O:1]=[C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][C:6]([C:13]([NH:45][O:44][CH:39]3[CH2:40][CH2:41][CH2:42][CH2:43][O:38]3)=[O:15])=[CH:7][CH:8]=2)[NH:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 196042892,4-Dihydroxyquinazoline-7-carboxylic acid

Product 1

HCID 866642012,4-dioxo-N-(tetrahydro-2H-pyran-2-yloxy)-1,2,3,4-tetrahydroquinazoline-7-carboxamideYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylic acid (0.15 g, 0.73 mmol), DMF (2.80 mL), triethylamine (0.30 mL, 2.2 mmol) and fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (0.25 g, 0.95 mmol) was stirred for 15 min and O-(tetrahydropyran-2-yl)hydroxylamine (0.10 g, 0.87 mmol) was added. The reaction mixture was stirred at rt for 1 d. Water was added and the mixture was extracted with EtOAc (2×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (50% to 100% EtOAc/hexanes) to afford 2,4-dioxo-N-(tetrahydro-2H-pyran-2-yloxy)-1,2,3,4-tetrahydroquinazoline-7-carboxamide (0.15 g, 68%). LC-MS: (FA) ES+ 306.

Workup

  1. stirringThe reaction mixture was stirred at rt for 1 d
  2. extractionthe mixture was extracted with EtOAc (2×)
  3. washThe combined organic phases were then washed with water, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash silica gel chromatography (50% to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-69ef4a07c99641daae4a46b6e765bad0
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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