Tert-Butylamine → 2-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-one

HRID 1055813Notes

Reaction equation

[C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].Cl[C:7]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[C:9](=[C:10]([I:19])[CH:11]=[CH:12][CH:13]=2)[N:8]=1>C1COCC1>[C:1]([NH:5][C:7]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[C:9](=[C:10]([I:19])[CH:11]=[CH:12][CH:13]=2)[N:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

A heterogeneous mixture of tert-butylamine (22.83 mL, 217 mmol) and 2-chloro-8-iodo-3-methylquinazolin-4(3H)-one (700) (4.64 g, 14.48 mmol) in 2 mL of THF in a 100 mL RBF fitted with a reflux condenser was heated in an oil bath at 50° C. for 4 h. The reaction mixture was concentrated under reduced pressure and the brown solid was dissolved in 300 mL of EtOAc, washed sequentially with 10 mL of water, 10 mL of sat. NaHCO3 solution and 10 mL of brine. The organic solution was concentrated. The residue was purified on a silica gel column (25-55% EtOAc in hexanes) to afford 2-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-one (4.64 g, 12.99 mmol, 90% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.12 (1H, dd, J=7.5, 1.3 Hz), 7.93 (1H, dd, J=7.8, 1.2 Hz), 6.89 (1H, t, J=7.6 Hz), 6.02 (1H, s), 3.41 (3H, s), 1.60 (9H, s). m/z (ES, +ve) 358.1 (M+H)+.

Workup

customRBF fitted with a reflux condenser
concentrationThe reaction mixture was concentrated under reduced pressure
dissolutionthe brown solid was dissolved in 300 mL of EtOAc
washwashed sequentially with 10 mL of water, 10 mL of sat. NaHCO3 solution and 10 mL of brine
concentrationThe organic solution was concentrated
customThe residue was purified on a silica gel column (25-55% EtOAc in hexanes)

Sources & evidence

ORD record: ord-da4be8cb3f764e41a091d988a5779283
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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