反应详情

To a stirred mixture of 4,7-Dichloroquinazoline (800 mg, 4 mmol) and piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (1.2 g, 5.2 mmol), as prepared in Example 1b, in a sealed vial at rt was added drop-wise a 1 M solution of LiHMDS in THF (6 mL, 6 mmol). The mixture was stirred at rt overnight. It was then quenched with aqueous NaH2PO4 and the mixture was extracted with DCM. The DCM layer was drawn off, washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to obtain 2.2 g (>100%) of crude 4-(7-chloro-quinazolin-4-yl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (29a) as a yellow semi-solid which was used as such for the next step.

1. customas prepared in Example 1b
2. customIt was then quenched with aqueous NaH2PO4
3. extractionthe mixture was extracted with DCM
4. washwashed with water, brine
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo