Title of Invention | "A PROCESS FOR THE PREPARATION OF CYCLOPENTA[G] QUINAZOLINE OF FORMULA(I)" |
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Abstract | A process for the preparation of a cyclopenta[g]quinazoline of formula (I): wherein: R is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 halogenoalkyl or C1-4 cyanoalkyl; or R is a group A(CH2)P where A is R°O or R0R1N wherein R0 and R1 are each independently hydrogen, C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or C1-4 cyanoalkyl, or R0 and R1 together with the intermediate N form a five- or six-membered heterocyclic ring and p is an integer in the range 0 to 4; and Ar1 is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C1-4 alkyl and C1-4 alkoxy; or an ester or amide thereof; comprising the step of reacting an ester or amide of formula (II): wherein R and Ar1 are as defined above and X is an alkoxy, aryloxy or optionally substituted amino group; or a protected derivative thereof; with a complex containing the (propargyl)Co2(CO)6+ ion, in an anhydrous organic solvent in a presence of abase. |
Full Text | DESCRIPTION (COMPLETE) & CLAIMS OCR NOT PREPARE DUE TO PRINT PROBLEM We claim: 1. A process for the preparation of a cyclopenta[g]quinazoline of formula (I): (Formula Removed) wherein: R is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 halogenoalkyl or C1-4 cyanoalkyl; or R is a group A(CH2)P where A is R0O or R0R1N wherein R0 and R1 are each independently hydrogen, C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or C1-4 cyanoalkyl, or R° and R1 together with the intermediate N form a five- or six-membered heterocyclic ring and p is an integer in the range 0 to 4; and Ar1 is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C1-4 alkyl and C1-4 alkoxy; or an ester or amide thereof; comprising the step of reacting an ester or amide of formula (II): (Formula Removed) wherein R and Ar1 are as defined above and X is an alkoxy, aryloxy or optionally substituted amino group; or a protected derivative thereof; with a complex containing the (propargyl)Co2(CO)6+ ion, in an anhydrous organic solvent in a presence of a base. 2. A process as claimed in claim 1 wherein the protecting derivative of the compound of the formula (II) is a compound in which hydroxyl groups and/or amino groups, other than that at N10, are protected to prevent reacton with the (propargyl)Co2(CO)6+ ion. 3 A process as claimed in claim 1 wherein the complex containing the (propargyl)Co2(CO)6+ ion is the tetrafluoroborate salt of formula (propargyl)Co2(CO)6+ BF4-. 4. A process as claimed in any preceding claim wherein the reaction is performed at temperatures ranging between -30°C to room temperature under argon. 5. A process as claimed in any preceding claim wherein the ester or amide of formula (II) is made by ring-closing a compound of formula (III): (Formula Removed) wherein R, Ar1 and X are as defined in claim 1; or a protected derivative thereof. 6. A process as claimed in claim 5 wherein the ring closure reaction is carried out in basic conditions in the presence of hydrogen peroxide. 7. A process as claimed in any preceding claim wherein X is a residue of an aliphatic alcohol of up to 6 carbon. 8. A process as claimed in any preceding claim wherein: R is C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or a group A(CH2)P, wherein R0 and R1 are each independently hydrogen or C1-4 alkyl; and Ar1 is 1, 4-phenylene which may optionally bear one or two substituents selected from the group consisting of chloro, fluoro, thiophene-2,5-diyl, thiazole-2,5-diyl and pyridine-2,5-diyl. 9. A process as claimed in any preceding claim wherein p is 1. 10. A process as claimed in any preceding claim wherein the cyclopenta[g]quinazoline of formula (I) or ester or amide thereof is further reacted to prepare a cyclopenta[g]quinazoline of formula (VI): (Formula Removed) wherein A and Ar1 are as defined above, and R3 is a group of the formula: (Formula Removed) in which A5 is a C1-6 alkylene group and R is hydrogen, C1-4 alkyl, C3-4 alkenyl or C3-4, alkynyl; Y4 is carboxy, tetrazol-5-yl, N-(C1-4alkylsulfonyl)carbamoyl, N-(phenylsulfonyl)-carbamoyl which may optionally bear one or two substituents on the phenyl ring selected from the group consisting of halogeno, nitro, C1-4 alkyl and C1-4 alkoxy, tetrazol-5-ylthio, tetrazol-5-ylsulfinyl or tetrazol-5-ylsulfonyl; and Y5 is the residue of a naturally occurring amino acid NH2CH(CO2H)Y5; or Y5 is a group of the formula: (Formula Removed) in which A4 is a C2-6 alkylene group; or Y5 is a group of the formula: (Formula Removed) in which A6 is a bond between the a-carbon atom, of the group —A5—CON(R)CH(Y4)— and Ar3 or is a C1-2 alkylene group; Ar3 is phenylene, tetrazolediyl, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which in the case of phenylene may optionally bear one or two substituents on the ring selected from halogeno, nitro, C1-4 alkyl and C1-4 alkoxy; A7 is a C1-3 alkylene or C2-3 alkenylene group; and Y6 is carboxy, tetrazol-5-yl, N-(C1-4 alkylsulfonyl)carbamoyl, N-(phenyl-sulfonyl)carbamoyl which may optionally bear one or two substituents on the phenyl ring selected from the group consisting of halogeno, nitro, C1-4 alkyl and C1-4 alkoxy, tetrazol-5-ylthio, tetrazol-5-ylsulfinyl or tetrazol-5-ylsulfonyl; the compound (VI) optionally being in the form of a pharmaceutically acceptable salt or |
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475-DELNP-2004-Abstract-(11-02-2011).pdf
475-DELNP-2004-Claims-(11-02-2011).pdf
475-DELNP-2004-Correspondence Others-(01-09-2011).pdf
475-DELNP-2004-Correspondence Others-(22-03-2011).pdf
475-DELNP-2004-Correspondence Others-(30-06-2011).pdf
475-DELNP-2004-Correspondence-Others-(11-02-2011).pdf
475-DELNP-2004-Correspondence-Others-(27-09-2010).pdf
475-DELNP-2004-Correspondence-Others-(29-03-2010).pdf
475-delnp-2004-correspondence-others.pdf
475-DELNP-2004-Description (Complete)-(11-02-2011).pdf
475-delnp-2004-description (complete).pdf
475-DELNP-2004-Form-1-(11-02-2011).pdf
475-DELNP-2004-Form-2-(11-02-2011).pdf
475-DELNP-2004-Form-3-(01-09-2011).pdf
475-DELNP-2004-Form-3-(22-03-2011).pdf
475-DELNP-2004-Form-3-(27-09-2010).pdf
475-DELNP-2004-Form-3-(29-03-2010).pdf
475-DELNP-2004-GPA-(11-02-2011).pdf
475-DELNP-2004-Petition -137-(11-02-2011).pdf
Patent Number | 249039 | ||||||||||||
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Indian Patent Application Number | 475/DELNP/2004 | ||||||||||||
PG Journal Number | 39/2011 | ||||||||||||
Publication Date | 30-Sep-2011 | ||||||||||||
Grant Date | 26-Sep-2011 | ||||||||||||
Date of Filing | 27-Feb-2004 | ||||||||||||
Name of Patentee | BTG INTERNATIONAL LIMITED | ||||||||||||
Applicant Address | 10 FLEET PLACE, LIMERBURNER LANE, LONDON EC4M 7SB, ENGLAND | ||||||||||||
Inventors:
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PCT International Classification Number | C07D 239/70 | ||||||||||||
PCT International Application Number | PCT/GB2002/03967 | ||||||||||||
PCT International Filing date | 2002-08-30 | ||||||||||||
PCT Conventions:
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