US4172200A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the preparation of 10-deazaaminopterin and related compounds
Assignee: Southern Research Institute
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Filing: 1978-06-15
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Granted: 1979-10-23
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Expires: 1998-06-15
Abstract
Abstract There is disclosed an improved process for the preparation of 10-deazaaminopterin and related compounds. In accordance with this process, 6-(bromomethyl)-2,4-pteridinediamine hydrobromide is reacted with triphenylphosphine to form a phosphonium salt which is then treated with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl)methylenetriphenylphosphorane. This compound is reacted with an aromatic aldehyde such as diethyl 4-formylbenzoyl-L-glutamate to form an olefin which is then reduced catalytically to the tetrahydro derivative of the desired product. Oxidation of the tetrahydro derivative is accomplished with hydrogen peroxide.
Inventors
- 👤 James R. Piper
- 👤 John A. Montgomery
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 19:15
CPC Classifications
C; C07; C07D; C07D475/00; C07D475/06; C07D475/08
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
113 words
A process which comprises reacting 6-(bromomethyl)-2,4-pteridinediamine hydrobromide with triphenylphosphine to form the phosphonium salt thereof; treating said phosphonium salt with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl) methylenetriphenylphosphorane; and reacting said ylid with an aromatic aldehyde having the formula: ##STR3## wherein R is a member selected from the group consisting of H, CO 2 R 1 or CO 2 H, CONHCH(CO 2 R 1 )(CH 2 ) 2 CO 2 R 2 or CONHCH(CO 2 H)(CH 2 ) 2 --CO 2 H in which R 1 and R 2 may each be a lower alkyl group, to obtain a product having the formula: ##STR4## wherein R is the same as previously described.
Claim 2
Dependent Claim
113 words
A process which comprises reacting 6-(bromomethyl)-2,4-pteridinediamine hydrobromide with triphenylphosphine to form the phosphonium salt thereof; treating said phosphonium salt with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl) methylenetriphenylphosphorane; and reacting said ylid with an aromatic aldehyde having the formula: ##STR3## wherein R is a member selected from the group consisting of H, CO 2 R 1 or CO 2 H, CONHCH(CO 2 R 1 )(CH 2 ) 2 CO 2 R 2 or CONHCH(CO 2 H)(CH 2 ) 2 --CO 2 H in which R 1 and R 2 may each be a lower alkyl group, to obtain a product having the formula: ##STR4## wherein R is the same as previously described.
Claim 3
Dependent Claim
11 words
A process as defined in claim 1 wherein R is hydrogen.
Claim 4
Dependent Claim
26 words
A process as defined in claim 1 wherein R is CO 2 H or CO 2 R 1 wherein R 1 is a lower alkyl group.
Claim 5
Dependent Claim
32 words
A process as defined in claim 1 wherein R is CONHCH(COR 1 )(CH 2 ) 2 CO 2 R 2 wherein R 1 and R 2 are each a lower alkyl group.
Claim 6
Dependent Claim
16 words
A process as defined in claim 4 wherein R 1 and R 2 are each ethyl.
Claim 7
Dependent Claim
19 words
A process as defined in claim 1 wherein R is CONCH(CO 2 H)(CH 2 ) 2 CO 2 H.
Claim 8
Dependent Claim
17 words
A process as defined in claim 1 wherein said reaction is conducted in an anhydrous inert solvent.
Claim 9
Dependent Claim
26 words
A process as defined in claim 1 wherein the product obtained by said process is reduced to form the corresponding tetrahydro derivative having the formula: ##STR5##
Claim 10
Dependent Claim
14 words
A process as defined in claim 8 wherein said reduction is accomplished by hydrogenation.
Claim 11
Dependent Claim
21 words
A process as defined in claim 8 wherein said tetrahydro derivative is oxidized to obtain a product having the formula: ##STR6##
Claim 12
Dependent Claim
19 words
A process as defined in claim 10 wherein oxidation is accomplished by treating said tetrahydro derivative with hydrogen peroxide.
Claim 13
Dependent Claim
64 words
A process for the preparation of 10-deazaaminopterin which comprises reacting 6-(bromomethyl)-2,4-pteridinediamine hydrobromide with triphenylphosphine to form the phosphonium salt thereof; treating said phosphonium salt with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl)methylenetriphenylphosphorane; reacting said ylid with diethyl 4-formylbenzoyl-L-glutamate to form diethyl N-[4-[2-(2,4-diamino-6-pteridinyl)vinyl]benzoyl]-L-glutamate; hydrogenating and hydrolyzing said diethyl N-[4-[2-(2,4-diamino-6-pteridinyl)vinyl]benzoyl]-L-glutamate to yield the tetrahydro derivative of 10-deazaaminopterin; oxidizing said tetrahydro derivative and recovering said 10-deazaaminopterin.
Claim 14
Dependent Claim
64 words
A process for the preparation of 10-deazaaminopterin which comprises reacting 6-(bromomethyl)-2,4-pteridinediamine hydrobromide with triphenylphosphine to form the phosphonium salt thereof; treating said phosphonium salt with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl)methylenetriphenylphosphorane; reacting said ylid with diethyl 4-formylbenzoyl-L-glutamate to form diethyl N-[4-[2-(2,4-diamino-6-pteridinyl)vinyl]benzoyl]-L-glutamate; hydrogenating and hydrolyzing said diethyl N-[4-[2-(2,4-diamino-6-pteridinyl)vinyl]benzoyl]-L-glutamate to yield the tetrahydro derivative of 10-deazaaminopterin; oxidizing said tetrahydro derivative and recovering said 10-deazaaminopterin.
References Cited (Backward Citations)
US4077957A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1982-10-22 | 1983-04-23 | 1983-10-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-10-22 | 1987-04-23 | 1987-10-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-10-22 | 1991-04-23 | 1991-10-23 | $7700.00 | Window Closed / Lapsed |