US4818819A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the preparation of fused pyridine compounds
Assignee: Princeton University
•
Filing: 1986-10-20
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Granted: 1989-04-04
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Expires: 2006-10-20
Abstract
Abstract 2-Amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-en-1-yl]pyrido[2,3,-d]pyrimidines and 2-amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-yn-1-yl]pyrido[2,3-d]pyrimidines are prepared through the reaction of a haloaromatic compound and an unsaturated compound in the presence of a palladium catalyst. The products are chemical intermediates for the preparation of antineoplastic agents. A typical embodiment is the reaction of a protected 2-amino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine and an ester of 4-iodobenzoic acid.
Inventors
- 👤 Edward C. Taylor
- 👤 George S. K. Wong
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 22:51
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
151 words
In the process of preparing a compound of the formula: ##STR14## wherein R 1 is --NHCH(COOR 2 )CH 2 CH 2 COOR 2 or OR 2 ; R 2 is hydrogen or a carboxylic acid protecting group; R 4 is hydrogen or an amino protecting group; Z 1 when taken independently of Z 2 is hydrogen; and Z 2 when taken independently of Z 1 is hydrogen, methyl or ethyl; or Z 1 and Z 2 when taken together are a carbon-carbon bond; the steps of allowing an unsaturated compound of the formula: ##STR15## wherein R 4 , Z 1 and Z 2 are as defined above, to react with a haloaromatic compound of the formula: ##STR16## wherein R 1 and R 2 are as defined aboved and X is bromo or iodo, in the presence of a palladium catalyst and in the presence or absence of an inert polar solvent.
Claim 2
Dependent Claim
151 words
In the process of preparing a compound of the formula: ##STR14## wherein R 1 is --NHCH(COOR 2 )CH 2 CH 2 COOR 2 or OR 2 ; R 2 is hydrogen or a carboxylic acid protecting group; R 4 is hydrogen or an amino protecting group; Z 1 when taken independently of Z 2 is hydrogen; and Z 2 when taken independently of Z 1 is hydrogen, methyl or ethyl; or Z 1 and Z 2 when taken together are a carbon-carbon bond; the steps of allowing an unsaturated compound of the formula: ##STR15## wherein R 4 , Z 1 and Z 2 are as defined above, to react with a haloaromatic compound of the formula: ##STR16## wherein R 1 and R 2 are as defined aboved and X is bromo or iodo, in the presence of a palladium catalyst and in the presence or absence of an inert polar solvent.
Claim 3
Dependent Claim
24 words
The process according to claim 1 wherein said palladium catalyst is generated from a triarylphosphine, a palladium halide salt, and a cuprous halide salt.
Claim 4
Dependent Claim
32 words
The process according to claim 2 in which R 1 is OR 2 , and R 2 contains a chiral center and is in one chiral form substantially free of the other.
Claim 5
Dependent Claim
17 words
The process according to claim 2 wherein R 1 is alkoxy of 1 to 10 carbon atoms.
Claim 6
Dependent Claim
11 words
The process according to claim 4 wherein R 1 is tert.-butoxy.
Claim 7
Dependent Claim
23 words
The process according to claim 4 wherein R 4 is alkanoyl of 2 to 10 carbon atoms inclusive of the carbonyl carbon atom.
Claim 8
Dependent Claim
11 words
The process according to claim 6 wherein R 4 is pivaloyl.
Claim 9
Dependent Claim
16 words
The process according to claim 2 wherein the reaction is conducted in acetonitrile as a solvent.
Claim 10
Dependent Claim
107 words
In the process of preparing a compound of the formula: ##STR17## wherein R 1 is --NHCH(COOR 2 )CH 2 CH 2 COOR 2 or OR 2 ; R 2 is hydrogen or a carboxylic acid protecting group; and R 4 is hydrogen or an amino protecting group; the step of allowing an unsaturated compound of hte fromula: ##STR18## wherien R 4 is as defined above, to react with a haloaromatic compund of the formula: ##STR19## wherein R 1 and R 2 are as defined above and X is bromo or ido, in the presence of a palladium catalyst and in the presence of an inert polar solvent.
Claim 11
Dependent Claim
107 words
In the process of preparing a compound of the formula: ##STR17## wherein R 1 is --NHCH(COOR 2 )CH 2 CH 2 COOR 2 or OR 2 ; R 2 is hydrogen or a carboxylic acid protecting group; and R 4 is hydrogen or an amino protecting group; the step of allowing an unsaturated compound of hte fromula: ##STR18## wherien R 4 is as defined above, to react with a haloaromatic compund of the formula: ##STR19## wherein R 1 and R 2 are as defined above and X is bromo or ido, in the presence of a palladium catalyst and in the presence of an inert polar solvent.
Claim 12
Dependent Claim
24 words
The process according to claim 9 wherein said palladium catalyst is generated from a triarylphosphine, a palladium halide salt, and a cuprous halide salt.
Claim 13
Dependent Claim
32 words
The process according to claim 9 in which R 1 is OR 2 , and R 2 contains a chiral center and is in one chiral form substantially free of the other.
Claim 14
Dependent Claim
17 words
The process according to claim 9 wherein R 1 is alkoxy of 1 to 10 carbon atoms.
Claim 15
Dependent Claim
11 words
The process according to claim 12 wherein R 1 is tert.-butoxy.
Claim 16
Dependent Claim
23 words
The process according to claim 12 wherein R 4 is alkanoyl of 2 to 10 carbon atoms inclusive of the carbonyl carbon atom.
Claim 17
Dependent Claim
11 words
The process according to claim 12 wherein R 4 is pivlaoyl.
Claim 18
Dependent Claim
16 words
The process according to claim 9 wherein the reaction is conducted in acetonitrile as a solvent.
Claim 19
Dependent Claim
22 words
The process according to claim 9 in which a 2-alkamido-4-hydroxy-6-ethynylpyrido pyrimidine is allowed to react with a dialkyl easter of N-(4-iodo-benzoyl)L-glutamic acid.
Claim 20
Dependent Claim
21 words
The process according to claim 2, in which a 2-alkamido-4-hydroxy-6-ethynylpyridopyrimidine is allowed to react with a dialkyl ester of N-(4-bromo-benzoyl)L-glutamic acid.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-04-03 | 1992-10-03 | 1993-04-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-04-03 | 1996-10-03 | 1997-04-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-04-03 | 2000-10-03 | 2001-04-04 | $7700.00 | Window Closed / Lapsed |