Title of Invention

"A PROCESS FOR THE PREPARATION OF CYCLOPENTA[G] QUINAZOLINE OF FORMULA(I)"

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
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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

Documents:

475-DELNP-2004-Abstract-(11-02-2011).pdf

475-delnp-2004-abstract.pdf

475-DELNP-2004-Claims-(11-02-2011).pdf

475-delnp-2004-claims.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-1.pdf

475-delnp-2004-form-18.pdf

475-DELNP-2004-Form-2-(11-02-2011).pdf

475-delnp-2004-form-2.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-form-3.pdf

475-delnp-2004-form-5.pdf

475-DELNP-2004-GPA-(11-02-2011).pdf

475-delnp-2004-gpa.pdf

475-delnp-2004-pct-304.pdf

475-delnp-2004-pct-308.pdf

475-delnp-2004-pct-409.pdf

475-delnp-2004-pct-416.pdf

475-DELNP-2004-Petition -137-(11-02-2011).pdf

abstract.jpg


Patent Number 249039
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:
# Inventor's Name Inventor's Address
1 VASSILIOS BAVETSIAS 3 CHIDDINGSTONE CLOSE, SUTTON, SURREY SM2 6NS, ENGLAND
PCT International Classification Number C07D 239/70
PCT International Application Number PCT/GB2002/03967
PCT International Filing date 2002-08-30
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 0121214.1 2001-08-31 U.K.
2 60/340,244 2001-12-18 U.K.