Tert-Butylamine → 8-bromo-2-(tert-butylamino)-3-cyclopropylquinazolin-4(3H)-one

HRID 1056422Notes

Reaction equation

HRID 1056422 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]1[CH2:15][CH2:14]1)[C:7]2=[O:16].[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>>[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]1[CH2:15][CH2:14]1)[C:7]2=[O:16]

Participants

3

Reactant 2

HCID 6385Tert-ButylamineHCID 897823358-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one

Product 1

HCID 897850258-bromo-2-(tert-butylamino)-3-cyclopropylquinazolin-4(3H)-oneYield 94%

Conditions

Temperature
90 °C

Procedure

8-bromo-2-chloro-3-cyclopropylquinazolin-4(3H)-one (723) (213 mg, 0.711 mmol) was treated with tert-butylamine (0.90 mL, 8.56 mmol) and heated at 90° C. in a sealed tube for 24 h. The reaction mixture was concentrated to remove the excess t-BuNH2 and the crude residue was chromatographed on an ISCO Combiflash RF (12 g Redisep column, using a gradient of 0-5% MeOH in DCM) affording 8-bromo-2-(tert-butylamino)-3-cyclopropylquinazolin-4(3H)-one (224 mg, 0.66 mmol, 94% yield) as an off-white crystalline solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (1H, dd, J=8.0, 1.4 Hz), 7.82 (1H, dd, J=7.7, 1.5 Hz), 6.94 (1H, t, J=7.7 Hz), 5.42 (1H, s), 2.62-2.71 (1H, m), 1.61 (9H, s), 1.28-1.35 (2H, m), 0.87-0.95 (2H, m). m/z (ESI, +ve) 335.9/337.9 (M+1)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove the excess t-BuNH2
  3. customthe crude residue was chromatographed on an ISCO Combiflash RF (12 g Redisep column

Sources & evidence

ORD record
ord-9b3a8cd58b4e4205b4b6a40f00799e38
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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