EnamineStore Blog

Larotrectinib Retrosynthesis

Larotrectinib (VITRAKVI®, Loxo Oncology Inc. and Bayer) is an inhibitor of receptors TrkA, TrkB, and TrkC which was approved by FDA for adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment on November 26, 2018.

Synthesis of this small molecule may be realized starting from these Building Blocks:

Larotrectinib retrosynthesis

 

Here are some analogs and similar Building Blocks, available from stock:

(3R,5S)-5-ethylpyrrolidin-3-ol hydrochloride 5,5-dimethylpyrrolidin-3-ol 5-methylpyrrolidin-3-ol 5-cyclopropylpyrrolidin-3-ol hydrochloride 5-azaspiro[3.4]octan-7-ol hydrochloride 1-azaspiro[4.4]nonan-3-ol hydrochloride 5-cyclohexylpyrrolidin-3-ol 1-azaspiro[4.5]decan-4-ol 1-azaspiro[4.4]nonan-4-ol rac-(2R,3R)-2-(propan-2-yl)pyrrolidin-3-ol hydrochloride, cis 4-azaspiro[2.4]heptan-7-ol hydrochloride (2S,3S)-2-methylpyrrolidin-3-ol hydrochloride 2,2-dimethylpyrrolidin-3-ol 1-azaspiro[4.6]undecan-4-ol 4,4-difluoropyrrolidin-3-ol hydrochloride (3R,4R)-4-fluoropyrrolidin-3-ol hydrochloride (S)-3-hydroxypyrrolidine hydrochloride 3-azabicyclo[3.1.0]hexan-1-ol hydrochloride 2,2,4,4-tetramethylpyrrolidin-3-ol rac-(3R,3aR,6aS)-octahydrocyclopenta[b]pyrrol-3-ol hydrochloride octahydro-1H-indol-3-ol hydrochloride, Mixture of diastereomers 3-tert-butylpyrrolidin-3-ol hydrochloride 3-(propan-2-yl)pyrrolidin-3-ol hydrochloride 3-cyclopropylpyrrolidin-3-ol 3-ethylpyrrolidin-3-ol hydrochloride 3-methylpyrrolidin-3-ol hydrochloride 3-(difluoromethyl)pyrrolidin-3-ol hydrochloride 3-(trifluoromethyl)pyrrolidin-3-ol rac-(3R,4S)-4-cyclopropylpyrrolidin-3-ol hydrochloride, trans 6-azaspiro[3.4]octan-8-ol hydrochloride 5-azaspiro[2.4]heptan-7-ol hydrochloride 4-ethylpyrrolidin-3-ol 4-methylpyrrolidin-3-ol, Mixture of diastereomers 4,4-dimethylpyrrolidin-3-ol hydrochloride piperidin-3-ol6-bromo-3-iodopyrazolo[1,5-a]pyrimidine 6-bromo-3-iodopyrazolo[1,5-a]pyrimidine ethyl 6-bromopyrazolo[1,5-a]pyrimidine-3-carboxylate 6-bromo-2-methylpyrazolo[1,5-a]pyrimidine 3-bromo-5-methylpyrazolo[1,5-a]pyrimidine 3-BROMO-6-METHYLPYRAZOLO[1,5-A]PYRIMIDINE 3-bromo-2-methylpyrazolo[1,5-a]pyrimidine 6-bromo-3-iodo-2-methylpyrazolo[1,5-a]pyrimidine hydrochloride 3-BROMO-7-CHLOROPYRAZOLO[1,5-A]PYRIMIDINE 7-chloropyrazolo[1,5-a]pyrimidine 5-chloropyrazolo[1,5-a]pyrimidine 6-chloropyrazolo[1,5-a]pyrimidine 6-bromopyrazolo[1,5-a]pyrimidine 6-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine 5-bromopyrazolo[1,5-a]pyrimidine 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine 6-bromo-2-iodopyrazolo[1,5-a]pyrimidine 5-chloro-3-iodopyrazolo[1,5-a]pyrimidine 3-bromopyrazolo[1,5-a]pyrimidine ethyl 6-bromopyrazolo[1,5-a]pyrimidine-2-carboxylate 3-methylpyrazolo[1,5-a]pyrimidine-5-carboxylic acid 7-chloro-3,5-dimethylpyrazolo[1,5-a]pyrimidinerac-(1R,5R)-1-phenyl-2-azabicyclo[3.2.0]heptane 1-phenyl-2-azabicyclo[2.1.1]hexane hydrochloride 2-phenyl-2-(trifluoromethyl)pyrrolidine 2-(4-fluorophenyl)pyrrolidine 2-(3-fluorophenyl)pyrrolidine hydrochloride 2-(3-fluorophenyl)-3-methylpyrrolidine 2-(3-fluorophenyl)-4-methylpyrrolidine 2-(4-methylphenyl)pyrrolidine 2-(3-methylphenyl)pyrrolidine 2-methyl-2-phenylpyrrolidine 2-phenylpyrrolidine 2-(2,5-difluorophenyl)pyrrolidine hydrochloride 3-methyl-2-phenylpyrrolidine, Mixture of diastereomers 4-methyl-2-phenylpyrrolidine, Mixture of diastereomers 2-(2-methylphenyl)pyrrolidine 2-(4-fluoro-2-methylphenyl)pyrrolidine 2-(3,5-difluorophenyl)pyrrolidine 4-fluoro-2-phenylpyrrolidine 2-[2-(trifluoromethyl)phenyl]pyrrolidine hydrochloride 2-[2-fluoro-3-(trifluoromethyl)phenyl]pyrrolidine hydrochloride 2-[4-(propan-2-yl)phenyl]pyrrolidine 2-(4-tert-butylphenyl)pyrrolidine 2-(2,6-difluoro-3-methylphenyl)pyrrolidine hydrochloride 2-(3,4-difluorophenyl)pyrrolidine hydrochloride 4-fluoro-2-(3-fluorophenyl)pyrrolidine hydrochloride, Mixture of diastereomers 2-(2,3,5-trifluorophenyl)pyrrolidine hydrochloride 2-(2,4-difluorophenyl)pyrrolidine hydrochloride 2-(2-fluorophenyl)-4-methylpyrrolidine, Mixture of diastereomers