Water → HCID 18008933, compound

Participants

Reaction Conditions

Reaction Steps

3-Bromo propionyl bromide (262 μl) was added to a stirred suspension of 3-(1-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinoxalin-6-yl)-propionic acid ethyl ester (0.229 g, Reference Example 1) and triethylamine (680 μl) in tetrahydrofuran (10 ml) cooled to 0° C. under argon atmosphere. After stirring at 0° C. for 1 hour then at 20° C. overnight the mixture was treated with 3-bromo propionyl bromide (90 μl) and stirring was continued for 2 hours at 21° C. The reaction mixture was treated with water (25 ml) and after stirring for 15 minutes at 20° C. the mixture was extracted three times with ethyl acetate (25 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate (10 ml), then washed four times with water (10 ml), then dried over magnesium sulfate and then evaporated to dryness under reduced pressure (40° C., 40 mbar). The residue (1.7 g) was subjected to flash chromatography on silica (50 g, 0.040-0.063 mm particle size) eluting with a mixture of cyclohexane and ethyl acetate (1:1, v/v) to give the title compound as a yellow foam (550 mg). TLC: RF=30/72, silica, eluting with a mixture of dichloromethane and methanol (9:1, v/v). 1H NMR [400 MHz, (CD3)2SO, at a temperature of 373° K.]: δ1.20 (t, J=7 Hz, 3H); 2.28 (s,, 3H); 2.64 (t, J=7.5 Hz, 2H); 2.91 (t, J=7.5 Hz, 2H); 3.81 (s, 3H); 3.84 (s, 2H); 3.87 (m, 2H); 3.93 (m, 2H); 4.11 (q, J=7 Hz, 2H); 5.68 (dd, J=10.5 and 2 Hz, 1H); 6.21 (dd, J=17 and 2 Hz, 1H); 6.38 (dd, J=17 and 10.5 Hz, 1H); 6.58 (broad d, J=8 Hz, 1H); 6.75 (broad s, 1H); 6.99 (broad t, J=7.5 Hz, 1H); from 7.10 to 7.25 (m, 4H); 7.57 (d, J=8.5 Hz, 1H); 7.69 (broad d, J=8 Hz, 1H); 7.92 (d, J=8.5 Hz, 1H); 8.18 (broad s, 1H); 8.28 (broad s, 1H). MS (EI): 584 (M+).

Provenance & Evidence