反应详情

To a solution of 1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine (100 mg, 0.33 mmol, 1.00 equiv) in methanol (5 ml) was added 2-methylpropanal (50 mg, 0.69 mmol, 2.00 equiv) at room temperature and the reaction solution was stirred for 1 h. Then NaBH3CN (45 mg, 0.72 mmol, 2.00 equiv) was added and stirred overnight at ambient temperature. The resulting solution was diluted with EtOAc (100 mL), washed with brine, dried over sodium sulfate and concentrated under vacuum. The crude product (120 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 54.0% in 13 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give 75 mg (63%) of the desired 1-N-methyl-1-N-(2-methylpropyl)-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine as a white solid. MS: (ES, m/z): 359 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.23 (s, 1H), 4.07-4.09 (m, 1H), 3.02 (t, 2H), 2.99 (t, 2H), 2.54-2.59 (m, 3H), 2.37-2.39 (m, 5H), 2.18-2.21 (m, 2H), 1.95-1.99 (m, 2H), 1.81-1.85 (m, 1H), 1.45-1.61 (m, 4H), 1.01 (s, 6H).

1. stirringstirred overnight at ambient temperature
2. washwashed with brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated under vacuum
5. customThe crude product (120 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
6. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 54.0% in 13 min)
7. customThe product-containing fractions were collected
8. custompartially evaporated
9. customto remove water and CH3CN under reduced pressure
10. waitThe residue was lyophilized overnight