13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 11 can be useful in the preparation of halinchondrin analogs.
C07D 307/28 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07F 7/08 - Compounds having one or more C—Si linkages
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 7 can be useful in the preparation of halinchondrin analogs such as Eribulin.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07D 307/28 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
4.
A CONTINUOUS FLOW PROCESS FOR THE PREPARATION OF INGENOL-3-MEBUTATE
Disclosed is a continuous process for the preparation of ingenol-3-mebutate by reaction, in solution, of ingenol or ingenol anion and angelic anhydride or an equivalent angelylating agent. The continuous flow process is preferably performed in the presence of a base such as lithium hexamethyl disilazane (LiHMDS) and/or an activating agent such as dicyclohexylcarbodiimide (DCC). Also disclosed is a process for recycling the other reaction products obtained in the continuous process for preparation of ingenol-3-mebutate for formation of ingenol, which can then be recycled to form ingenol-3-mebutate.
C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
C07C 67/48 - SeparationPurificationStabilisationUse of additives
C07C 69/533 - Monocarboxylic acid esters having only one carbon-to-carbon double bond
5.
CRYSTALLINE DERIVATIVES OF (S)-1-((2R,3R,4S,5S)-5-ALLYL-3-METHOXY-4-(TOSYLMETHYL)TETRAHYDROFURAN-2-YL)-3-AMINOPROPAN-2-OL
Disclosed are salts of a compound of formula 1, as shown below, where R1, R2, R3, R4, R5, R6 and R7 are as described herein. Also, disclosed is a process for the preparation of the salts of the compounds of formula 1, and intermediates used therein. The salts of the compound of formula 1 can be useful for preparation of halichondrin analogs such as eribulin.
C07C 69/76 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring
6.
SYNTHETIC PROCESS FOR PREPARATION OF MACROCYCLIC C1-KETO ANALOGS OF HALICHONDRIN B AND INTERMEDIATES USEFUL THEREIN INCLUDING INTERMEDIATES CONTAINING -SO2-(P-TOLYL) GROUPS
Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, R7, R7', R8, R9, R10, R11, R12 and R13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed.
C07D 307/28 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
7.
3-((2S,5S)-4-METHYLENE-5-(3-OXOPROPYL)TETRAHYDROFURAN-2-YL)PROPANOL DERIVATIVES, THEIR PREPARATION AND INTERMEDIATES USEFUL THEREOF
Discloses is a process for preparation of a compound of formula 11, or a derivative thereof, wherein PG1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 11 can be useful in the preparation of halinchondrin analogs.
C07D 307/28 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
The specification relates to a process for preparation of an antifolate compound of formula 7, such as Pralatrexate. Also, disclosed are intermediates and processes for preparation of intermediates useful in the preparation of the antifolate compound. The substituents Y, Z, R, R1 and R2 are as described herein. The processes and intermediates can provide an alternate route to the synthesis of the antifolate compound. Further, the processes can help to avoid distillation or evaporation of high boiling point solvents, chromatographic purification and use of hazardous combination of solvents; and can also provide a product having high purity, all of which are desirable for synthesis on a large scale.
C07D 475/08 - Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms
C07D 239/95 - QuinazolinesHydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
C07C 69/612 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
9.
PROCESS FOR PREPARATION OF 17-SUBSTITUTED STEROIDS
The specification relates to a process for preparation of 17-substituted steroid and intermediates useful therein. Embodiments of 17-substituted steroid have been shown as useful for treatment of androgen-dependent disorders, especially prostatic cancer, and also oestrogen-dependent5 disorders such as breast cancer.
C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
C07J 75/00 - Processes for the preparation of steroids, in general
C07J 9/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
10.
SYNTHETIC PROCESS FOR PREPARATION OF MACROCYCLIC C1-KETO ANALOGS OF HALICHONDRIN B AND INTERMEDIATES USEFUL THEREIN
Disclosed is a compound of formula (1), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, R7, R7', R8, R9, R10, R11, R12 and R13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and5 intermediates used therein. The compound of formula (1) can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula (1) is also disclosed.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Disclosed is a compound of formula (1), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, R7, R7', R8, R9, R10, R11, R12 and R13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and5 intermediates used therein. The compound of formula (1) can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula (1) is also disclosed.
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
2-((2S,3S,4R,5R)-5-((S)-3-AMINO-2-HYDROXYPROP-1-YL)-4-METHOXY-3-(PHENYLSULFONYLMETHYL)TETRAHYDROFURAN-2-YL)ACETALDEHYDE DERIVATIVES AND PROCESS FOR THEIR PREPARATION
Disclosed is a compound of formula 1, as shown below, where R1, R2, R3, R4, R5, R6 and R7 are as described herein. Also, disclosed is a process for the preparation of compounds of formula 1, and intermediates used therein. The compound of formula 1 can be useful for preparation of halichondrin analogs such as Eribulin.
C07H 9/02 - Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07H 7/00 - Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
13.
2-((2S,3S,4R,5R)-5-((S)-3-AMINO-2-HYDROXYPROP-1-YL)-4-METHOXY-3-(PHENYLSULFONYLMETHYL)TETRAHYDROFURAN-2-YL)ACETALDEHYDE DERIVATIVES AND PROCESS FOR THEIR PREPARATION
Disclosed is a compound of formula 1, as shown below, where R1, R2, R3, R4, R5, R6 and R7 are as described herein. Also, disclosed is a process for the preparation of compounds of formula 1, and intermediates used therein. The compound of formula 1 can be useful for preparation of halichondrin analogs such as Eribulin.
C07H 9/02 - Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
C07H 7/00 - Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
14.
PROCESS FOR PREPARATION OF 3-((2S,5S)-4-METHYLENE-5-(3-OXOPROPYL)TETRAHYDROFURAN-2-YL) PROPANOL DERIVATIVES AND INTERMEDIATES USEFUL THEREOF
Discloses is a process for preparation of a compound of formula 7, or a derivative thereof, wherein PG1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 7 can be useful in the preparation of halinchondrin analogs such as Eribulin.
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
The specification relates to compounds and process for the preparation of a compound of formula 7, where LG is a leaving group and hal is a halide and is Cl, Br or I. The compound of formula 7 can be useful in the preparation of natural products, such as halichondrin and its derivatives.
C07C 309/73 - Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
C07D 493/22 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
17.
Carbanucleoside synthesis and novel intermediate compounds useful therein
Anti-virally active carbanucleosides such as entecavir are prepared by a process which utilizes, throughout the synthesis, an aromatic protectant group for the hydroxyl and the alkyl hydroxy groups of the starting material, removed as the final step of a multi-step synthesis. Such protectant groups yield intermediates which are solid and therefore easily purified at various stages of the process, for an economical and relatively fast process for synthesizing the final product.
Disclosed is a process for preparing a treprostinil salt. The process involves the step of dissolving treprostinil in a water-miscible organic solvent to form a treprostinil solution. The treprostinil solution is reacted with an aqueous basic solution containing an alkali metal cation to form treprostinil salt. Allowing crystallization of the treprostinil salt to take place, and then collecting the treprostinil salt formed.
A process for preparation of a compound of formula (I) or or a pharmaceutically acceptable salt, ester, or prodrug thereof, is disclosed. The process involves hydrogenating, in the presence of a catalyst, a compound of formula (II). The different substituents are as described in the specification. Also disclosed are intermediates and processes for their preparation. Further, the process can provide an alternate route for the synthesis of Vernakalant from starting materials that can be readily available.
A process for preparation of a compound of formula I or a pharmaceutically acceptable salt thereof, is disclosed. The process involves subjecting a compound of formula II to Ullmann-type conditions to effect an intra-molecular ring closure reaction to form the compound of formula I. The different substituents are as described in the specification. Further, the process can provide an alternate route for the synthesis of asenapine from starting materials that can be readily available.
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07C 39/373 - Halogenated derivatives with all hydroxy groups on non-condensed rings and with unsaturation outside the aromatic rings
Treprostinil is prepared by a process which involves Pauson - Khan cyclization of an an alkene-substituted, alkyne-substituted benzene corresponding to formula : (I) where PMB represents para-methoxy benzyl protecting group and R1 and R2 are alcohol protecting groups. Following cyclization, the resulting compound can be subjected to several chemical transformations followed by alkylation, hydrolysis and salt formation to yield treprostinil sodium. The use of para-methoxybenzyl group as the phenolic protecting group confers several process advantages that result in simplified purification of the final product and improved yields.
C07C 49/755 - Unsaturated compounds containing a keto group being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
C07C 41/08 - Preparation of ethers by addition of compounds to unsaturated compounds by addition of organic compounds only to carbon-to-carbon triple bonds
C07C 43/215 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring having unsaturation outside the six-membered aromatic rings
C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
C07C 45/50 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
C07C 45/67 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton
C07C 49/84 - Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
C07C 51/367 - Preparation of carboxylic acids or their salts, halides, or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
C07C 59/72 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
22.
PROTECTED ALDEHYDES FOR USE AS INTERMEDIATES IN CHEMICAL SYNTHESES, AND PROCESSES FOR THEIR PREPARATION
A para-methoxy protected benzaldehyde useful in preparation of treprostinil, and of formula:(Formula (1)) is prepared by subjecting to Claisen re-arrangement a substituted benzaldehyde of formula (la): (Formula (Ia)) to form the m-hydroxy-substituted benzaldehyde of formula (lb): (Formula (Ib)) and then reacting compound (lb) with a p-methoxybenzyl (PMB) compound to form a PMB-substituted benzaldehyde of formula (1).
C07C 47/575 - Compounds having —CHO groups bound to carbon atoms of six-membered aromatic rings containing ether groups, groups, groups, or groups
C07C 45/67 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton
23.
PROCESS FOR THE SYNTHESIS OF CARBONUCLEOSIDE AND INTERMEDIATES FOR USE THEREIN
Disclosed is a process for preparing a carbonucleoside of formula (1) and intermediates for use therein. The process involves the step of reacting a compound of formula (2) with a compound of formula (3) under Mitsunobu-type reaction conditions to obtain a compound of formula (4), wherein PG1, PG2, PG3 and PG4 are protecting groups. The compound of formula (4) is deprotected to form the compound of formula (1), as shown below.
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
24.
CARBANUCLEOSIDE SYNTHESIS AND NOVEL INTERMEDIATE COMPOUNDS USEFUL THEREIN
Anti-virally active carbanucleosides such as entecavir are prepared by a process which utilizes, throughout the synthesis, an aromatic protectant group for the hydroxyl and the alkyl hydoxy groups of the starting material, removed as the final step of a multi-step synthesis. Such protectant groups yield intermediates which are solid and therefore easily purified at various stages of the process, for an economical and relatively fast process for synthesizing the final product.
C07D 239/47 - One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
C07D 319/08 - 1,3-DioxanesHydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
C07D 473/00 - Heterocyclic compounds containing purine ring systems
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 473/34 - Nitrogen atom attached in position 6, e.g. adenine
25.
PROCESS FOR THE SYNTHESIS OF CARBONUCLEOSIDE AND INTERMEDIATES FOR USE THEREIN
Disclosed is a process for preparing a carbonucleoside of formula 1 and intermediates for use therein. The process involves the step of reacting a compound of formula 2 with a compound of formula 3 under Mitsunobu-type reaction conditions to obtain a compound of formula 4, wherein PG is a protecting group. The compound of formula 4 is deprotected to form the compound of formula 1, as shown below. (see formula 2) (see formula 3) (see formula 4) (see formula 1)
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
26.
PREPARATION OF INTERMEDIATES FOR THE SYNTHESIS OF DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS
4- (2,3- dichlorophenyl) -1,4- dihydro- 2,6- dimethyl- 5- methoxycarbonyl- 3- pyridinecarboxylic acid, a key intermediate in the synthesis of the cardiovascular calcium channel blocker drug 3-butanoyloxymethoxycarbonyl-5- methoxycarbonyl-4- (2,3-dichlorophenyl) -2,6- dimethyl-1,4- dihydropyridine, of purity greater than 97% and essentially free of the corresponding diacid, is prepared by a process involving selective precipitation of its carboxylate via addition of concentrated solutions of alkali metal salts. Similar intermediate mono-carboxylic acids useful in the synthesis of other unsymmetrically substituted dihydropyrine drugs such as nisoldipine, nitrendipine and nimodipine can be similarly prepared and purified.
The current application relates to a process for preparing O3-(butanoyloxymethyl)-O5-methyl-4-(2, 3-dichlorophenyl)-2,6-dimethyl-1,4- dihydropyridme-3,5-dicarboxylate, clevidipine butyrate, by alkylation of 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-5- methoxycarbonyl-3-pyridinecarboxylic acid with tetramethylammonium hydroxide and chloromethyl butyrate in a dioxane/water solvent. The final product is purified by crystallization in a mixed solvent system of dichloromethane/heptane or lsopropanol/water.
1 a-hydroxy vitamin D2 (doxercalciferol) of exceptionally high purity and stability is prepared by a process involving chromatographically purifying 1 α-hydroxyvitamin D2 monoacetate, chemically removing the acetate protectant group from the purified product to form 1 α-hydroxyvitamin D2, and precipitating the 1 a- hydroxyvitamin D2 so formed from a mixed organic solvent consisting essentially of at least one C1 - C6 dialkyl ether or C1 - C6 alkyl ester, and at least one C5 - C12 hydrocarbon.
C07C 401/00 - Irradiation products of cholesterol or its derivativesVitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
patents
