反应详情

To a stirred solution of 2′-chloro-9′-cyclopentyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepin]-6′(5′H)-one (Intermediate 131; 15 g, 51.24 mmol) in DMA (1 L) under nitrogen was added methyl iodide 3.51 mL, 56.36 mL). The mixture was cooled in ice/water to 4° C. Sodium hydride (60% mineral oil dispersion; 2.26 g, 56.36 mmol) was added in one portion. A small exotherm to 6° C. was observed. The reaction mixture was stirred on an ice/water bath for 1 hour, the cooling bath was removed and the reaction stirred at room temperature overnight. Solvent was evaporated in vacuo and the residue treated with water. This afforded a solid, which was filtered off and washed with water to give an off white solid, which was crystallised from IPA (100 mL) with hot filtration through fluted paper to remove a small amount insoluble matter. The crystallised material was filtered, washed with chilled IPA, and dried by dessication under high vacuum at room temperature over the weekend to give the title compound as a white crystalline solid (12.78_g, 81%)

1. customto 6° C.
2. customthe cooling bath was removed
3. stirringthe reaction stirred at room temperature overnight
4. customSolvent was evaporated in vacuo
5. additionthe residue treated with water
6. customThis afforded a solid, which
7. filtrationwas filtered off
8. washwashed with water
9. customto give an off white solid, which
10. customwas crystallised from IPA (100 mL) with hot filtration
11. customto remove a small amount insoluble matter
12. filtrationThe crystallised material was filtered
13. washwashed with chilled IPA
14. customdried by dessication under high vacuum at room temperature over the weekend