Diisopropylethylamine → tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(9aR)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate

To a solution of crude (9aR)-octahydropyrazino[2,1-c][1,4]oxazine dihydrochloride (1.7185 g, 7.99 mmol) in DMF (40 mL) was added tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (3.97 g, 7.98 mmol) and N,N-diisopropylethylamine (4.60 mL, 26.41 mmol). The solution was stirred overnight and then diluted with Et2O (200 mL). The mixture was washed with water (2×100 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (100 mL). The combined organic phase was washed with a fresh portion of water (50 mL), and then dried over anhydrous Na2SO4. The mixture was filtered, concentrated in vacuo, and the residue was dissolved in DCM (200 mL) and dried over anhydrous Na2SO4. The mixture was filtered, and the solution was concentrated in vacuo. The residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N) to afford tris(1,1-dimethylethyl)2-{2-chloro-5-fluoro-6-[(9aR)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (4.34 g, 90%) as a white foam. LCMS: (M+H)+: 603.3.

1. washThe mixture was washed with water (2×100 mL)
2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (100 mL)
3. washThe combined organic phase was washed with a fresh portion of water (50 mL)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationThe mixture was filtered
6. concentrationconcentrated in vacuo
7. dissolutionthe residue was dissolved in DCM (200 mL)
8. dry with materialdried over anhydrous Na2SO4
9. filtrationThe mixture was filtered
10. concentrationthe solution was concentrated in vacuo
11. customThe residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N)

ORDレコード

ord-ca12ed211d45448db72fc3c86705357b

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07893056B2