Tert-Butylamine → 8-bromo-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)quinazolin-4(3H)-one

HRID 1056387Notes

Reaction equation

HRID 1056387 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]([CH2:13][CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[C:7]2=[O:24].[C:25]([NH2:29])([CH3:28])([CH3:27])[CH3:26]>>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:29][C:25]([CH3:28])([CH3:27])[CH3:26])[N:8]([CH2:13][CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[C:7]2=[O:24]

Participants

3

Reactant 2

HCID 6385Tert-ButylamineHCID 897821118-bromo-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-2-chloro-quinazolin-4(3H)-one

Product 1

HCID 897852468-bromo-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)quinazolin-4(3H)-oneYield 89%

Conditions

Temperature
130 °C

Procedure

A solution of 8-bromo-3-(3-((tert-butyldimethylsilyl)oxy)propyl)-2-chloroquinazolin-4(3H)-one (500a; 0.080 g, 0.185 mmol) in tert-butylamine (Aldrich; 0.584 mL, 5.56 mmol) was sealed and heated in a biotage initiator microwave at 100° C. for 30 min, 130° C. for 30 min, and 150° C. for 60 min. The reaction was partitioned between satd aq sodium bicarbonate and DCM. The aqueous layer was extracted with DCM 3 times, and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 8-bromo-2-(tert-butylamino)-3-(3-((tert-butyldimethylsilyl)oxy)propyl)quinazolin-4(3H)-one (0.077 g, 0.164 mmol, 89% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.05 (1H, dd, J=8.0, 1.4 Hz), 7.85 (1H, dd, J=7.6, 1.4 Hz), 6.97 (1H, t, J=7.8 Hz), 5.24 (1H, s), 4.10 (2H, t, J=7.1 Hz), 3.75 (2H, t, J=5.4 Hz), 1.85-1.99 (2H, m), 1.62 (9H, s), 0.95 (9H, s), 0.12 (6H, br. s.). m/z (ESI, +ve ion) 468.0/470.0 (M+H)+.

Workup

  1. customThe reaction was partitioned between satd aq sodium bicarbonate and DCM
  2. extractionThe aqueous layer was extracted with DCM 3 times
  3. dry with materialthe combined organics were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-30334676fe8a46068a6d50ed34f965e6
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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