反应详情

A mixture of (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid methyl ester (Example 211; 32 mg, 0.06 mmol) and lithium hydroxide monohydrate (11 mg, 0.262 mmol) in methanol/tetrahydrofuran/water (2:2:1; 0.25 mL) was stirred at room temperature for 48 h. An additional portion of lithium hydroxide monohydrate (6 mg, 0.14 mmol) was added and the solution was stirred for an additional 4 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) and re-evaporated. A solution of the residual material in the same solvent mixture (1 mL) was applied to a silica gel column. The column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6). The appropriate homogeneous fractions were combined, evaporated and then lyophilized to give (Z)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]-3-(quinolin-3-yl)propenoic acid (18 mg, 58% yield).

1. stirringthe solution was stirred for an additional 4 h
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. dissolutionthe residue was dissolved in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6)
4. customre-evaporated
5. washThe column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6)
6. customevaporated