10-06-2021 дата публикации
Номер: US20210171522A1
Принадлежит:
The present disclosure relates to derivatives (e.g., hydroxyl, keto, glucuronide, sulfonic acid, and deuterated) of a Fibroblast Growth Factor Receptors (FGFR) inhibitor, including methods of preparation thereof, and intermediates in the preparation thereof, which are useful in the treatment of FGFR mediated disease such as cancer. 1. A compound which is selected from:3-(2,6-difluoro-3-hydroxy-5-methoxyphenyl)-1-ethyl-8-(morpholinomethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-2-one; and3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-4-hydroxy-8-(morpholinomethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-2-one, or a pharmaceutically acceptable salt thereof.2. The compound of claim 1 , which is 3-(2 claim 1 ,6-difluoro-3-hydroxy-5-methoxyphenyl)-1-ethyl-8-(morpholinomethyl)-1 claim 1 ,3 claim 1 ,4 claim 1 ,7-tetrahydro-2H-pyrrolo[3′ claim 1 ,2′:5 claim 1 ,6]pyrido[4 claim 1 ,3-d]pyrimidin-2-one claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , which is 3-(2 claim 1 ,6-difluoro-3 claim 1 ,5-dimethoxyphenyl)-1-ethyl-4-hydroxy-8-(morpholinomethyl)-1 claim 1 ,3 claim 1 ,4 claim 1 ,7-tetrahydro-2H-pyrrolo[3′ claim 1 ,2′:5 claim 1 ,6]pyrido[4 claim 1 ,3-d]pyrimidin-2-one claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein one C—H group is replaced with a C—X group.8. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein the N—H group is replaced with an N—X group.9. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein the O—H group is replaced with an O—X group.10. A compound which is 3-(2 claim 4 ,6-difluoro-3 claim 4 ,5-bis(methoxy-d3)phenyl)-1-ethyl-8-(morpholinomethyl)-1 claim 4 ,3 claim 4 ,4 claim 4 ,7-tetrahydro-2H-pyrrolo[3′ claim 4 ,2′:5 claim 4 ,6]pyrido[4 claim 4 ,3-d]pyrimidin-2-one claim 4 , or a pharmaceutically ...
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