PROCESS FOR THE PREPARATION OF HU-910 AND CRYSTALLINE STRUCTURE THEREOF

• US 20190315669A1
• Filed: 11/13/2017
• Published: 10/17/2019
• Est. Priority Date: 11/13/2016
• Status: Abandoned Application

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: ADAM, Jean-Michel, DOTT, Pascal, HOHLER, Marcus, BURGER, Tanja, TAGLIENTE, Orazio, MISCHLER, Ernst
• Application Number:
  US16/347,838
• Publication Number:
  US 20190315669A1
• Time in Patent Office: Days
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 253/30 by reactions not involving the formation of cyano groups
• CPC Class Codes: C07C 255/37 the carbon skeleton being further substituted by etherified hydroxy groups
• CPC Class Codes: C07C 255/40 the carbon skeleton being further substituted by doubly-bound oxygen atoms
• CPC Class Codes: C07C 2602/42 the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 303/28 by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
• CPC Class Codes: C07C 309/66 Methanesulfonates
• CPC Class Codes: C07C 41/16 by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
• CPC Class Codes: C07C 41/20 by hydrogenation of carbon-to-carbon double or triple bonds
• CPC Class Codes: C07C 41/26 by introduction of hydroxy or O-metal groups
• CPC Class Codes: C07C 41/30 by increasing the number of carbon atoms, e.g. by oligomerisation
• CPC Class Codes: C07C 41/40 by change of physical state, e.g. by crystallisation
• CPC Class Codes: C07C 43/2055 containing more than one ether bond
• CPC Class Codes: C07C 43/215 having unsaturation outside the six-membered aromatic rings
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 45/44 by reduction and hydrolysis of nitriles
• CPC Class Codes: C07C 47/277 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 51/09 from carboxylic acid esters or lactones
• CPC Class Codes: C07C 51/60 by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
• CPC Class Codes: C07C 62/34 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 67/08 : by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• CPC Class Codes: C07C 67/343 : by increase in the number of carbon atoms
• CPC Class Codes: C07C 69/757 : having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety

Abstract

The invention provides processes for the preparation of HU-910, which are scalable to industrial purposes, using safer reagents and having high yield and pure product and a crystalline structure of HU-910, which is a unique product thereof.

Claims

1-23. -23. (canceled)

24. A process for the preparation of HU-910 including the steps of:

(a) Preparation of resorcinol building block comprising;

25. The process of claim 24, wherein step 1 comprises the reactions:

(1a) dimethylation reaction;

(1b) a reduction reaction;

(1c) a Wittig reaction and (1d) a hydrogenation reaction.

26. The process of claim 24, wherein step 2 comprises the reactions:

(2a) esterification reaction (2b) deprotonation (2c) triflation reaction.

27. The process of claim 24, wherein step 3 comprises the reactions:

(3a) a deprotonation of the dimethoxyaryl ring (3b) a reaction of the generated arylmetal with an electrophile (3c) a C—

C coupling reaction.

28. The process of claim 24, wherein step 4 comprises a hydrolysis step.

29. The process of claim 24, wherein step 4 comprises the reactions:

(4a) a hydrolysis reaction (4b) an acid reduction.

30. The process of claim 24, wherein step 4 comprises the reactions:

(4a) a hydrolysis (4b) an acid chloride formation and (4c) a reduction.

31. A crystalline structure of ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en- 1-yl)methanol (HU-910) having the following unit cell:

a=33.098(7) A alpha=90 deg., b=7.1740(14) A beta=124.70(3) deg. and c=25.105(5) A gamma=90 deg.

32. A crystalline structure of HU-910 according to claim 31, having the following unit cell:

a=33.098(7) A alpha=90 deg., b=7.1740(14) A beta=124.70(3) deg. and c=25.105(5) A gamma=90 deg.