Water → 8-bromo-2-(tert-butylamino)-3-isopropylquinazolin-4(3H)-one

HRID 1056274Notes

Reaction equation

HRID 1056274 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([CH:13]([CH3:15])[CH3:14])[C:7]2=[O:16].[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18].O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:21][C:17]([CH3:20])([CH3:19])[CH3:18])[N:8]([CH:13]([CH3:15])[CH3:14])[C:7]2=[O:16]

Participants

5

Reactant 3

HCID 962WaterHCID 6385Tert-ButylamineHCID 897821108-Bromo-2-chloro-3-isopropyl-quinazolin-4-one

Product 1

HCID 897820438-bromo-2-(tert-butylamino)-3-isopropylquinazolin-4(3H)-oneYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A slurry of 8-bromo-2-chloro-3-isopropylquinazolin-4(3H)-one (406c, 0.40 g, 1.326 mmol) and tert-butylamine (4.18 mL, 39.8 mmol) was heated in a sealed tube at 80° C. overnight. The reaction was treated with ice, water, and DCM. The cloudy aq. layer was extracted 4×DCM and 1× EtOAc. The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (24 g column) using 0-40% EtOAc/hexanes. The product-containing fractions were concentrated to afford 8-bromo-2-(tert-butylamino)-3-isopropylquinazolin-4(3H)-one (0.39 g, 1.15 mmol, 87% yield) as an oil which slowly solidified. 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (1H, dd, J=7.9, 1.5 Hz), 7.83 (1H, dd, J=7.6, 1.4 Hz), 6.97 (1H, t, J=7.7 Hz), 5.55 (1H, br. s.), 4.68 (1H, br. s.), 1.63 (9H, s), 1.55 (6H, d, J=7.2 Hz). m/z (ESI, +ve) 338.0/340.0 (M+H)+.

Workup

  1. extractionThe cloudy aq. layer was extracted 4×DCM and 1× EtOAc
  2. dry with materialThe combined organics were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. additionThe material was treated with DCM
  6. custompurified by silica gel chromatography (24 g column)
  7. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-8c8ffc1ade5e4d369612e127522492a5
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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