Synthesis of ras inhibitors
AssigneeRevolution Medicines, Inc.
InventorsShaoling LI, Suresh Manthati, Ross Wang, Steve Ballmer, Xiaojun Huang
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Abstract
The present invention relates to Ras inhibitors and to methods for preparing Ras inhibitors.
Claims21
A method of preparing Compound 1:
- the method comprising:
- a) reacting Compound 1a and Compound 1b to form Compound 1c:
- b) oxidizing and hydrolyzing Compound 1c to form Compound 1d:
- and
- c) cyclizing Compound 1d to form Compound 1:
A compound having the structure of Formula II:
- or a salt thereof, wherein R1 is optionally substituted C1-C6 alkyl, optionally substituted 3- to 10-membered cycloalkyl, or optionally substituted C6-C10 aryl.
A method of preparing Compound 2a, the method comprising:
- a) esterifying Compound 2b to form Compound 2c:
- b) protecting and tosylating Compound 2c to form Compound 2d:
- and
- c) iodinating Compound 2d to form Compound 2a:
A method of preparing Compound 3:
- the method comprising:
- a) contacting Compound 3a and Compound 3b in the presence of a base to form Compound 3c:
- and
- b) hydrolyzing Compound 3c to form Compound 3:
A compound having the structure of Formula III, Compound 5, or Compound 6:
- or a salt thereof, wherein R is H or
A method of preparing Compound 6a, the method comprising:
- a) borylating Compound 7 to form Compound 4a:
- b) coupling Compound 4a and Compound 6b to form Compound 5a:
- and
- c) borylating Compound 5a to form Compound 6a:
A compound having the structure of Formula I:
- or a salt thereof, wherein R1 is H or C1-C6 alkyl.
A method of preparing Compound 9c:
- or a salt thereof, the method comprising:
- a) formylating Compound 9c-1 to form Compound 9c-2:
- b) condensing Compound 9c with malonic acid to form Compound 9c-3:
- c) aminating Compound 9c-3 to form Compound 9c-4 H2O:
- and
- d) protecting Compound 9c-4 to form Compound 9c:
A method of preparing Compound 9:
- the method comprises:
- a) coupling Compound 2a with Compound 9a to form Compound 9b:
- b) hydrolyzing Compound 9b to form Compound 9c:
- c) coupling Compound 9c and Compound 9d to form Compound 9e:
- d) deprotecting Compound 9e to form Compound 9f:
- e) coupling Compound 9f with Compound 3 to form Compound 9g:
- and
- f) hydrolyzing Compound 9g to form Compound 9:
A method of preparing Compound A:
- the method comprising:
- a) contacting Compound 6a with pinacol to form Compound 10:
- b) esterifying Compound 9 with Compound 10 to form Compound 11:
- and
- c) cyclizing Compound 11 to form Compound A:
A method of preparing Compound A:
- the method comprising the steps of:
- a) coupling Compound 6a and Compound 9 to form Compound 12:
- and
- b) lactonizing Compound 12 to form compound A:
A compound having the structure of Compound 10, Compound 11, or Compound 12:
- or a salt thereof.
Dependencies are inferred from the claim text.