Processes for preparing an FGFR inhibitor
AssigneePrincipia Biopharma Inc.
InventorsJiang Zhu, Mohammad Masjedizadeh
Life of this patent
Estimating the term…
Abstract
To an appropriate reactor equipped with mechanical stirrer was charged acetic acid (12 L), tert-butyl 4-(3-(6-(3,5-dimethoxyphenyl)-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)propyl)piperazine-1-carboxylate (2000 g) and triethylamine (639 g, 2.3 eq.). Internal temperature was adjusted to approximately 20° C. and N-chlorosuccinimide (1651 g, 4.5 eq.) was added at 20-30° C. Reaction was stirred for 2 hours. Ethyl acetate (30 L) was added. 5% aqueous NaCl solution (20 L) was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with 30% aqueous potassium carbonate solution (14 L). The organic layer was concentrated to ˜12 L and used for next step directly.
Claims7
A process of preparing a compound of formula (1):
- comprising:
- (G) reacting a compound of formula (e):
- where R is alkyl;
- with a compound of formula (f):
- and
- (H) treating a compound of formula (g) formed in situ
- from the reaction of compound (e) and (f) with a compound of formula (h) or a salt thereof
- under alkylating reaction conditions to provide a compound of formula (1), where PG in formula (1) and formula (h) is an amino protecting group.
A process for preparing a compound of formula (2) and/or (3):
- comprising reacting a compound of formula (1):
- with a N-chlorosuccinimide (NCS) to provide the compound of formula (2) and/or (3):
- where PG is an amino protecting group.
A process for preparing a compound of formula (4):
- comprising treating a compound of formula (2) and/or (3):
- with methylamine to give the compound of formula (4)
A process for preparing a compound of formula (5):
- or a salt thereof;
- comprising removing the amino protecting group “PG” of compound (4)
- to give the compound of formula (5):
- or a salt thereof.
A process of preparing a compound of formula (d) comprising reacting a compound of formula (6) with a compound of formula (iii) where LG is a leaving group under acylating reaction conditions
- to give a compound of formula (d);
- or
- reacting a compound of formula (6) with propenoic acid under amide bond formation reaction conditions:
- to give a compound of formula (d).
Dependencies are inferred from the claim text.