Synthesis of cerdulatinib
AssigneePortola Pharmaceuticals, Inc.
InventorsAnjali Pandey, Arvinder Sran, Ying Chen, Daniele Poggiali, Tiziano Fumagalli
Life of this patent
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Abstract
The present disclosure provides processes for the preparation of cerdulatinib, which is of formula I: or a salt thereof. The disclosure also provides intermediates and processes for the preparation of the intermediates useful in the preparation of cerdulatinib or a salt thereof.
Claims50
A process for preparing cerdulatinib, which is of formula I:
- or a salt thereof, the process comprises contacting Compound A or a salt thereof with Compound B or a salt thereof under conditions to form cerdulatinib or a salt thereof:
- wherein X is selected from the group consisting of Cl, Br, CH3S(O)— and CH3S(O)2—.
A three-step, one-pot process for preparing cerdulatinib or a salt thereof, comprising steps (1) contacting Compound F
- or a salt thereof with ammonia or a salt thereof to form Compound E
- or a salt thereof,
- (2) contacting Compound E or a salt thereof with cyclopropylamine or a salt thereof to form Compound A
- or a salt thereof, and
- (3) contacting Compound A or a salt thereof with Compound B
- or a salt thereof to form cerdulatinib or a salt thereof, wherein X is selected from the group consisting of Cl, Br, CH3S(O)— and CH3S(O)2—, X1 and X2 are independently a leaving group, and wherein all of steps (1)-(3) are conducted in one reactor without isolation of intermediates.
A three-step, one-pot process for preparing cerdulatinib or a salt thereof, comprising steps (1) contacting Compound F-1
- or a salt thereof with ammonia or a salt thereof to form Compound E-1
- or a salt thereof,
- (2) contacting Compound E-1 or a salt thereof with cyclopropylamine or a salt thereof to form Compound A-1:
- or a salt thereof, and
- (3) contacting Compound A-1 or a salt thereof with Compound B:
- or a salt thereof to form cerdulatinib or a salt thereof, wherein all of steps (1)-(3) are conducted in one reactor without isolation of intermediates.
A two-step, one-pot process for preparing cerdulatinib comprising step (1) contacting Compound C
- or a salt thereof with an oxidizing agent or a salt thereof, to form Compound A-2 or Compound A-3
- or a salt thereof, or a mixture thereof, and
- (2) contacting Compound A-2 or Compound A-3 or a salt thereof, or a mixture thereof, with Compound B
- or a salt thereof to form cerdulatinib or a salt thereof.
A process for preparing cerdulatinib HCl salt comprising contacting cerdulatinib with hydrochloric acid in a solvent comprising dimethyl sulfoxide and ethanol to form cerdulatinib HCl salt.
A compound of Formula A:
- or a salt thereof, wherein X is selected from the group consisting of Cl, Br, CH3S(O)— and CH3S(O)2—.
A compound selected from:
- or a salt thereof.
Dependencies are inferred from the claim text.