1-Methylcyclobutan-1-amine hydrochloride → 8-iodo-3-methyl-2-((1-methylcyclobutyl)amino)quinazolin-4(3H)-one

HRID 1055825Notes

Reaction equation

Cl.[CH3:2][C:3]1([NH2:7])[CH2:6][CH2:5][CH2:4]1.Cl[C:9]1[N:18]([CH3:19])[C:17](=[O:20])[C:16]2[C:11](=[C:12]([I:21])[CH:13]=[CH:14][CH:15]=2)[N:10]=1>C1COCC1.CCOC(C)=O>[I:21][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[N:10]=[C:9]([NH:7][C:3]1([CH3:2])[CH2:6][CH2:5][CH2:4]1)[N:18]([CH3:19])[C:17]2=[O:20]

Participants

Conditions

Temperature: 80 °C

Procedure

A heterogeneous mixture of 1-methylcyclobutanamine hydrochloride (Oakwood Chemical, cat #041889; 0.69 g, 5.70 mmol) (Oakwood Chemical, cat #041889), 2-chloro-8-iodo-3-methylquinazolin-4(3H)-one (700) (0.96 g, 3.0 mmol) and TEA (2.1 mL, 15.10 mmol) in 2 mL of THF in a sealed glass tube was heated in an oil bath at 80° C. for 4 h. The reaction mixture was diluted with EtOAc, washed with water followed by brine. The organic extract was concentrated and the residue was purified on a silica gel column (25-55% EtOAc in hexanes) to afford 8-iodo-3-methyl-2-((1-methyl-cyclobutyl)amino)quinazolin-4(3H)-one (0.94 g, 2.55 mmol, 85% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.11 (1H, dd, J=7.4, 1.4 Hz), 7.92 (1H, dd, J=7.8, 1.4 Hz), 7.03 (1H, s), 6.87 (1H, t, J=7.7 Hz), 3.40 (3H, s), 2.20-2.46 (4H, m), 1.88 (2H, m), 1.72 (3H, s). m/z (ESI, +ve) 370.1 (M+H)+).

Workup

washwashed with water
extractionThe organic extract
concentrationwas concentrated
customthe residue was purified on a silica gel column (25-55% EtOAc in hexanes)

Sources & evidence

ORD record: ord-5e221c498d1549c09e2e6740e7718e9b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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