Synthesis methods and intermediates for the production of remimbrutinib
AssigneeNovartis AG
InventorsAude FIGUCCIA, Lucie LOVELLE, Michael PARMENTIER
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Abstract
This invention relates to novel processes for synthesizing N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide and to intermediates which are used in such processes.
Claims44
A synthesis method comprising converting compound X6b and compound F6 into compound F7:
- wherein X and Y are each independently Cl, Br, or I, and wherein P is an amine protecting group.
(canceled)
16-19. (canceled)
(canceled)
30-31. (canceled)
(canceled)
A method for making a synthetic intermediate X6b:
- wherein X is F, Cl, Br, or I;
- the method comprising reacting compound X6d with compound N6a:
- wherein X is Cl, Br, or I.
39-69. (canceled)
The method of any preceding claim, wherein the method is used in the synthesis of compound F11:
71-74. (canceled)
A synthetic intermediate X6b:
- wherein X is Cl, Br, or I.
76:
- The method according to claim 20 wherein the borylation step is characterized by at least one of the following:
- xii. the catalyst is Pd(MeCN)2Cl2 in an amount of 0.5 mol % relative to the number of moles of X6b;
- xiii. the ligand is tBuPPh2 in an amount of 1 mol % relative to the number of moles of X6b;
- xiv. the catalyst is Pd(MeCN)2Cl2, the ligand is tBuPPh2 and the number of moles of tBuPPh2 is twice the number of moles of Pd(MeCN)2Cl2,
- xv. the borylating agent is bis(pinacolato)diboron in an amount of about 1.05 molar equivalents relative to X6b;
- xvi. the base is KOAc in an amount of 2.5 equivalents relative to X6b;
- xvii. the temperature of the borylation step is 60° C. or 70° C.
The method of claim 76 wherein the borylation step is:
Dependencies are inferred from the claim text.