Methods of preparing substituted pyrazolopyrimidines
AssigneeKSQ Therapeutics, Inc.
InventorJeremy Clinton WILT
Life of this patent
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Abstract
The present disclosure provides compounds having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein R1 is defined as set forth in the specification. The present disclosure also provides methods of preparing a compound of Formula (VI):
Claims78
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof;
- wherein
- R1 is selected from cyano, —CHO, —CH2NR2R3, and —CH2R4;
- R2 is selected from hydrogen, optionally substituted aryl, and optionally substituted heteroaryl;
- R3 is selected from hydrogen, amino, and —NR5R6;
- R4 is selected from Formula II and Formula III:
- R5 and R6 are individually selected from hydrogen and an amine protecting group;
- R7 is selected from optionally substituted aryl and optionally substituted heteroaryl;
- R8 is selected from carbonyl, alkoxy, and sulfonate;
- and
- R9 is selected from hydroxy, alkoxy, sulfonate, and a leaving group.
A compound of Formula IV:
- or a pharmaceutically acceptable salt thereof;
- wherein
- and
- R11 is hydrogen or alkyl.
A process for preparing a compound of Formula VI:
- comprising:
- reducing a compound of Formula V:
A process for preparing a compound of Formula Va:
- wherein R9 is a leaving group selected from trifluoromethanesulfonate, toluenesulfonate, methanesulfonate;
- comprising:
- reacting a compound of Formula VII:
- with toluenesulfonic anhydride, toluenesulfonyl chloride, methansulfonic anhydride, methansulfonyl chloride, trifluoromethanesulfonic anhydride, or trifluoromethanesulfonyl chloride to form a compound of Formula Va.
A process of preparing a compound of Formula VII:
- comprising:
- reacting a compound of Formula VIII:
- or a salt thereof,
- with an acid to form a compound of Formula VII,
- wherein R14 is an amine protecting group.
A process of preparing a compound of Formula VIII:
- or a salt thereof,
- comprising:
- coupling a compound of Formula IX:
- or a salt thereof,
- with (4-cyclopropyl-6-methoxypyrimidin-5-yl)boronic acid to form a compound of Formula VIII,
- wherein R14 is an amine protecting group.
A process of preparing a compound of Formula IX:
- or a salt thereof,
- comprising:
- reacting a compound of Formula X:
- or a salt thereof,
- with a 2,4-dichloropyrimidine-5-carboxylate ester to form a compound of Formula IX,
- wherein R14 is an amine protecting group.
A process of preparing a compound of Formula X:
- or a salt thereof,
- comprising:
- reacting a compound of Formula XI:
- with tert-butyl carbazate and a reducing agent to form a compound of Formula X.
A process of preparing a compound of Formula XI:
- comprising:
- reacting a compound of Formula XII:
- with a reducing agent to form a compound of Formula XI.
A process of preparing a compound of Formula XII:
- comprising:
- reacting a compound of Formula XIII:
- with an alkylating agent to form a compound of Formula XII.
A process of preparing a compound of Formula XIV:
- comprising:
- reacting a compound of Formula XV:
- or a salt thereof,
- with a compound of Formula XVI:
- to form a compound of Formula XIV.
A compound of Formula XVII:
- or a salt thereof.
A compound of Formula XX:
- or a salt thereof.
A compound of Formula XXVIII:
- or a salt thereof.
A compound of Formula XXVIV:
- or a salt thereof.
A compound of Formula XXX:
- or a salt thereof.
A process of preparing a compound of Formula XIV:
- comprising:
- reacting a compound of Formula X:
- or a salt thereof,
- with a compound of Formula XVI:
- to form a compound of Formula XIV;
- wherein R14 is an amine protecting group.
A process of preparing a compound of Formula XXX:
- comprising:
- reacting a compound of Formula XXVIV
- or a salt thereof,
- with a compound of Formula XVI:
- to form a compound of Formula XXX.
A process of preparing a compound of Formula XXVIV:
- or a salt thereof,
- comprising:
- reacting a compound of Formula XXVIII
- with acid to form a compound of Formula XXVIV or a salt thereof.
A process of preparing a compound of Formula XXVIII:
- or a salt thereof,
- comprising:
- reacting a compound of Formula XXVII:
- with tert-butyl carbazate and a reducing agent to form a compound of Formula XXVIII.
Dependencies are inferred from the claim text.