Acetic Acid → HCID 86664206, compound

HRID 1616178Notes

Reaction equation

HRID 1616178 reaction equation
Cl.[NH2:2][OH:3].[OH-].[K+].NO.[O:8]=[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19](OC)=[O:20])[CH:17]=2)[N:12]=[CH:11][N:10]1[C:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([CH3:25])[CH3:24].C(O)(=O)C>CO.CN(C=O)C>[OH:3][NH:2][C:19]([C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][N:10]([C:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([CH3:25])[CH3:24])[C:9]2=[O:8])=[O:20]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 787HydroxylamineHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67282966HCID 67282966, compound

Product 1

HCID 86664206HCID 86664206, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10.0 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6.0 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (2.0 mL, 3.5 mmol) was added to a solution of methyl 4-oxo-3-(2-phenylpropan-2-yl)-3,4-dihydroquinazoline-6-carboxylate (0.11 g, 0.35 mmol) in methanol (0.75 mL) and DMF (0.50 mL). After stirring for 4 h at rt, excess reagent was quenched by the addition of acetic acid (0.2 mL, 3.5 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford N-hydroxy-4-oxo-3-(2-phenylpropan-2-yl)-3,4-dihydroquinazoline-6-carboxamide (84 mg, 75%). LC-MS: (FA) ES+ 324; 1H NMR (400 MHz, DMSO) δ 11.25 (s, 1H), 9.11 (s, 1H), 8.72 (s, 1H), 8.36 (d, J=1.9 Hz, 1H), 8.14 (dd, J=8.5, 2.1 Hz, 1H), 7.76 (d, J=8.5 Hz, 1H), 7.34-7.14 (m, 5H), 1.96 (s, 6H).

Workup

  1. customA precipitate formed
  2. additionon mixing
  3. temperatureAfter heating at 90° C. for 30 minutes
  4. temperaturethe mixture was cooled to rt
  5. custompotassium salt and was carefully removed by syringe
  6. concentrationThe mixture was concentrated to dryness
  7. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-58dbd9f9a8e946e0a646dc6c09b5d00d
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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