Citric Acid → Cyclopropanesulfonic acid {17-[2-(3-fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carbonyl}-amide

温度

50 °C

A mixture of the acid 159 (200 mg, 0.324 mmol) and CDI (105 mg, 0.649 mmol) in dry THF (12 mL) was heated at reflux for 2 h under N2. The reaction mixture was cooled 50° C. and a pre-mixed solution of cyclopropyl sulfonamide (118 mg, 0.973 mmol) and DBU (138 μL, 0.908 mmol) in 2 ml of dry THF was added to the reaction mixture. The reaction was stirred at 50° C. for 18 h. The solution was pored in a separatory funnel and acidified with approx. 20 mL citric acid 10% (aq). Additional brine (20 mL) and EtOAc (40 mL) was added. The mixture was extracted with EtOAc and washed with brine, thereafter dried with Na2SO4, filtered and the solvent was removed by rotary evaporation. The crude product was purified by HPLC on an Ace-5 C8 column (100×21.2 mm) with a gradient going from 35 to 60% acetonitrile (0.1% TFA) in H2O (0.1% TFA) over 8 minutes. The title compound was obtained as a white solid (144 mg, 62%), LRMS (M+H) 720.

1. temperaturewas heated
2. temperatureat reflux for 2 h under N2
3. customThe solution was pored in a separatory funnel
4. extractionThe mixture was extracted with EtOAc
5. washwashed with brine
6. dry with materialdried with Na2SO4
7. filtrationfiltered
8. customthe solvent was removed by rotary evaporation
9. customThe crude product was purified by HPLC on an Ace-5 C8 column (100×21.2 mm) with a gradient
10. waitgoing from 35 to 60% acetonitrile (0.1% TFA) in H2O (0.1% TFA) over 8 minutes

ORDレコード

ord-e07ef61bca7c4ee5a1df93d2ee57648c

出典データセット

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07659245B2