PATENT CLAIM ANALYSIS

Application Number: 15995098
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2018-09
Patent Classification: ["546", "208000"]

Abstract:
The present invention discloses a preparation method of cobimetinib (XL518, GDC-0973) (I). The preparation steps include: taking (2S)-2-piperidinecarboxylic acid as the raw material, performing acyl cyanation, hydrolysis, esterification and Boc protection to obtain an intermediate [2-oxo-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)]acetate, performing an addition reaction, a reduction reaction and a cyclization reaction on the intermediate to obtain an intermediate (2S)-1-tert-butoxycarbonyl-2-(3-hydroxyazetidin-3-yl)piperidine, and performing a condensation reaction with a side chain to obtain the cobimetinib (I). The preparation method has the advantages of accessible raw materials, simple technique, high economy and environment friendliness, and is suitable for industrial production.

Claim (Index 1):
A preparation method of cobimetinib, the preparation steps including: performing an acyl cyanation reaction on (2S)-2-piperidinecarboxylic acid with thionyl chloride, a cyanation reagent and a phase-transfer catalyst, performing cyano hydrolysis on an obtained product, performing an esterification reaction with alcohol, and protecting piperidin amino by using di-tert-butyl dicarbonate to obtain [2-oxo-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)]acetate; performing an addition reaction on the [2-oxo-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)]acetate and nitromethane under the action of a catalyst to obtain [2-hydroxy-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)-3-nitro]propionate; sequentially performing ester group and nitro reduction reactions on the [2-hydroxy-2-((2 S)-1-tert-butoxycarbonylpiperidin-2-yl)-3-nitro]propionate to obtain [2-hydroxy-2-((2 S)-1-tert-butoxycarbonylpiperidin-2-yl)-3-amino]propanol; performing a cyclization reaction on the [2-hydroxy-2-((2S)-1-tert-butoxycarbonylpiperidin-2-yl)-3-amino]propanol under the actions of an azo reagent and an organic phosphine reagent to obtain (2S)-1-tert-butoxycarbonyl-2-(3-hydroxyazetidin-3-yl)piperidine; and performing a condensation reaction on the (2S)-1-tert-butoxycarbonyl-2-(3-hydroxyazetidin-3-yl)piperidine and 3,4-difluoro-2-[(2-chloro-4-iodophenyl)amino]benzoic acid under the actions of a condensing agent and an alkali accelerator to obtain the cobimetinib (I); wherein the alcohol in the esterification reaction is methanol, ethanol, n-propanol, isopropanol, allyl alcohol or benzyl alcohol.

Metadata:
- Claim Count in Document: 20.0
- Percentile: 93.0
- Lexical Diversity: 1.84507
- Patent Class: 546.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['15952202', '14975785', '15206553', '16345744', '15575171']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7646474212861861
- 35 USC 102 Novelty (BERT): 0.5171154021354276
- Combined Prediction Score: 0.7398942193711102
- Mean Citation Score: 259.266924
- Max Citation Score: 292.34512
- Similarity Product: 212.350125635376

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 1
- Claim Label 112: 0
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test