反应详情

温度

90 °C

A solution of 4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexan-1-amine (140 mg, 0.48 mmol, 1.00 equiv) in ethanol (20 mL) was added 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (72 mg, 0.49 mmol, 1.00 equiv) and KI (80 mg, 1.00 equiv) and the resulting solution was stirred for 8 h at 90° C. in an oil bath. After concentrated in vacuo, the crude product (160 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% HCOOH and CH3CN (6.0% CH3CN up to 52.0% in 14 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 the desired trans-1-(pyrrolidin-1-yl)-2-[(4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexyl)amino]ethan-1-one (14.4 mg) as a off-white solid and trans-2-[[2-oxo-2-(pyrrolidin-1-yl)ethyl](4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one (32.8 mg) as a off-white solid, respectively.

1. concentrationAfter concentrated in vacuo
2. customthe crude product (160 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
3. waitmobile phase, water with 0.05% HCOOH and CH3CN (6.0% CH3CN up to 52.0% in 14 min)
4. customThe product-containing fractions were collected
5. custompartially evaporated
6. customto remove water and CH3CN under reduced pressure
7. waitThe residue was lyophilized overnight