PATENT CLAIM ANALYSIS

Application Number: 16246999
Application Type: Utility
Filing Date: 2019-01
Publication Date: 2019-05
Patent Classification: ["549", "214000"]

Abstract:
The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Claim (Index 82):
A method of preparing an intermediate in the synthesis of eribulin, said method comprising:\n (A) cleaving the double bond in a compound of formula (VIIIA) to afford a compound of formula (VIIIB), the compound of formula (VIIIA) having the structure: wherein\n X 1  is oxo, or X 1 , together with the carbon atom to which it is attached, forms a ketal or \u2014(CH(OP 3 ))\u2014, wherein P 3  is H or a hydroxyl protecting group; \n R 1  is H or \u2014CH 2 OP 4 ; \n each of P 1 , P 2 , and P 4  is independently a hydroxyl protecting group, or P 1  and P 4 , together with the atoms to which each is attached, combine to form a cyclic protected diol; and \n the compound of formula (VIIIB) having the structure: (B) reacting the compound of formula (VIIIB) with a compound of formula (VIIIB-a) to afford a compound of formula (VIIIC): wherein R 2  is H or \u2014CH 2 CH 2 P 5 , and P 5  is a hydroxyl protecting group; and the compound of formula (VIIIB-a) has the following structure: (C) reacting the compound of formula (VIIIC) with a dehydrating agent to afford a compound of formula (VIIID): (D) reacting the compound of formula (VIIID) with a dihydroxylating agent to afford a compound of formula (VIIIE): (E) preparing a compound of formula (VIIIF) through a reaction sequence comprising reacting the compound of formula (VIIIE) with N-bromosuccinimide to afford a first intermediate, reacting said first intermediate with an acylating agent to afford a second intermediate, and (a), when R 2  is \u2014CH 2 CH 2 OP 5 , contacting said second intermediate with a reducing agent, or (b), when R 2  is H, allylating said second intermediate compound of formula (VIIIF): wherein Z is an ester or \u2014OP 7 , wherein P 7  is H or a hydroxyl protecting group, and R 3  is \u2014CH 2 CH 2 OP 5  or \u2014CH 2 CH\u2550CH 2 ; (F) reacting the compound of formula (VIIIF) with a 1,4-reducing agent to afford a compound of formula (VIIIG): and\n (G) forming a compound of formula (VIIIH) through a reaction sequence comprising reacting the compound of formula (VIIG) with a Br\u00f8nsted acid and Y\u2014H, wherein Y is optionally substituted C 1-6  alkyl, the compound of formula (VIIIH) having the following structure: \n wherein Y is optionally substituted C 1-6  alkyl ether; R 2  is \u2014CH 2 CH 2 OP 5 ; X 2  is oxo, or X 2 , together with the carbon to which it is attached, forms a ketal or \u2014(CH(OP 6 ))\u2014, wherein P 6  is a hydroxyl protecting group.

Metadata:
- Claim Count in Document: 20.0
- Percentile: 99.0
- Lexical Diversity: 1.88679
- Patent Class: 549.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15033970', '15707412', '15571921', '11874218', '14069057']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7300842274078149
- 35 USC 102 Novelty (BERT): 0.5867970695293129
- Combined Prediction Score: 0.7157555116199648
- Mean Citation Score: 425.015932
- Max Citation Score: 529.3929400000002
- Similarity Product: 394.132245128112

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

Dataset: test