Sodium Hydroxide → HCID 89793970, compound

HRID 1056410Notes

Reaction equation

HRID 1056410 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[N:8]([CH:13]1[CH2:16][CH2:15][CH2:14]1)[C:7]2=[O:17].P(Cl)(Cl)([Cl:20])=O.CCN(C(C)C)C(C)C.[OH-].[Na+]>O>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([Cl:20])[N:8]([CH:13]1[CH2:16][CH2:15][CH2:14]1)[C:7]2=[O:17]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 89793967HCID 89793967, compound

Product 1

HCID 89793970HCID 89793970, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 8-bromo-3-cyclobutylquinazoline-2,4(1H,3H)-dione (2.33 g, 7.89 mmol), phosphorous oxychloride (Acros Organics, Geel, Belgium; 3.68 ml, 39.5 mmol), and DIPEA (5.50 ml, 31.6 mmol) was heated over a 130° C. oil bath for 5 h. The reaction mixture was then cooled to RT and poured onto ice, and the resulting mixture was diluted with water (250 mL) to provide a brown suspension. 10N aqueous NaOH was added to the vigorously stirred suspension (maintaining the reaction mixture at 0° C.) until a pH of 10 was achieved. The precipitated solid was collected by vacuum filtration, washed with water (3×20 mL), and dried in vacuo to provide 8-bromo-2-chloro-3-cyclobutylquinazolin-4(3H)-one (1.888 g, 6.02 mmol, 76% yield) as a tan solid: 1H NMR (400 MHz, CDCl3) δ ppm 8.16 (1H, dd, J=8.0, 1.4 Hz), 7.99 (1H, dd, J=7.8, 1.4 Hz), 7.32 (1H, t, J=7.8 Hz), 5.22 (1H, quin, J=8.8 Hz), 2.89-3.05 (2H, m), 2.43-2.56 (2H, m), 1.98 (1H, q, J=10.7 Hz), 1.74-1.90 (1H, m). m/z (ESI, +ve) 313.0/314.9/316.9 (M+H)+.

Workup

  1. additionpoured onto ice
  2. customto provide a brown suspension
  3. temperaturemaintaining the reaction mixture at 0° C.) until a pH of 10
  4. filtrationThe precipitated solid was collected by vacuum filtration
  5. washwashed with water (3×20 mL)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-ecaf46f5945142f7a418c659c8f303cb
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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