Larotrectinib Sulfate synthesis

10synthesis methods

Product Name:Larotrectinib Sulfate
CAS Number:1223405-08-0
Molecular formula:C21H24F2N6O6S
Molecular Weight:526.52

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Yield:1223405-08-0 98.43%

Reaction Conditions:

with sulfuric acid in methanol at 20; for 0.5 h;Inert atmosphere;Solvent;Concentration;Temperature;

Steps:

3 Preparation of Amorphous Form AM(HS)

10422] To a solution of (S)-N-(5-((R)-2-(2,5-difluoro- phenyl)pyrrolidin-i -yl)pyrazolo[ 1 ,5-a]pyrimidin-3-yl)-3- hydroxypyrrolidine-i-carboxamide (9.40 g, 21.94 mmol) in MeOH (220 mE) was slowly added sulfuric acid (0.1 M in MeOH, 219.4 mE, 21.94 mmol) at ambient temperature under rapid stirring. Afier 30 minutes, the reaction was first concentrated by rotary evaporator to near dryness, then on high vacuum for 48 h to provide amorphous form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin- 1 -yl)pyrazolo[ 1 ,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-i -carboxamide sulfate (11.37 g, 21.59 mmol, 98.43% yield). ECMS (apci mlz 429.1, M+H).

References:

US2017/281632,2017,A1 Location in patent:Paragraph 0382; 0419; 0420; 0421; 0422