CA1082695A - Process for preparing adenosine-5'-carboxamides - Google Patents
Process for preparing adenosine-5'-carboxamidesInfo
- Publication number
- CA1082695A CA1082695A CA164,578A CA164578A CA1082695A CA 1082695 A CA1082695 A CA 1082695A CA 164578 A CA164578 A CA 164578A CA 1082695 A CA1082695 A CA 1082695A
- Authority
- CA
- Canada
- Prior art keywords
- adenosine
- ester
- alcohol
- amide
- reaction mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Abstract of the Disclosure An improved process for preparing adenosine-5'-carboxamides comprising reacting an ester of adenosine-5'-carboxylic acid, or an acid addition salt of the ester with an appropriate amine in the presence of an appropriate alcohol.
Description
~ 8 Z 6~ S
Detailed Description of ~he Invention This invention relates to an improved process for adellosine-5'-carboxamides.
Certain adenosine-5'-carboxamides have been ~ound to possess excellent cardiovascular activity (See German Patent No. 2,034~785). While there are available methods for preparing the compounds, they are generally useful only in small laboratory runs, and in some instances, it is extremely di~icult to obtain the desired compound. `. . ` `
L0 The present invention provides an improved process ~or preparing compounds of the formula > ~
Rl Nll ¦ `"
R2 l .. 1-~
. ' ~ j , OH OH
- ~ . , . . . " ~
1~82~5 wherein Rl and R2 ea.ch a.re selected from the group consist-ing of hydrogen, loweralkylJ lowerhaloalkyl, lowerhydroxyalkyl, lowercycloalkyl, loweralkylcycloalkyl, loweralkenyl, lower-haloalkenyl, lowerhydroxyalkenyl, loweralkynyl, lowerhalo-alkynyl, benzylamino, phenyl, loweralkylphenyl, loweralkoxy-loweralkyl, substituted phenyl, 2-methylfuran, di(Cl-C4)-alkylamino(Cl-C~)alkyl~ adamantyl or Rl and R2 taken together form a 5- or 6-membered heterocyclic moiety, Generally speaking, the process of thls invention comprises reacting an ester of adenosine-5'-carboxylic acid, or an acld addition salt of an ester of adenosine-5'-carboxylic ac d with an appropriate amine of the formula _,Rl or HNN ~ Rl .
in the presence of an appropriate alcohol.
15It is preferred that the ester or ester salt be suspended in a suitable alcohol such as methanol, ethanol, isopropanolJetc. and the amine is added to the alcohol suspension. The reaction proceeds best at temperatures above 70; however, it is preferred to reflux the reaction r~ 20 for a suitable length of time, ~ ~or at least 16 hours and usually for 16 to 18 hours. It is to be under- `
stood, however, that the reaction can be carried out for periods longer than 18 hours.
The amide is then recovered simply by, for exampleg ~.
concentrating the reaction to dryness and taking the residue .. ~ -
Detailed Description of ~he Invention This invention relates to an improved process for adellosine-5'-carboxamides.
Certain adenosine-5'-carboxamides have been ~ound to possess excellent cardiovascular activity (See German Patent No. 2,034~785). While there are available methods for preparing the compounds, they are generally useful only in small laboratory runs, and in some instances, it is extremely di~icult to obtain the desired compound. `. . ` `
L0 The present invention provides an improved process ~or preparing compounds of the formula > ~
Rl Nll ¦ `"
R2 l .. 1-~
. ' ~ j , OH OH
- ~ . , . . . " ~
1~82~5 wherein Rl and R2 ea.ch a.re selected from the group consist-ing of hydrogen, loweralkylJ lowerhaloalkyl, lowerhydroxyalkyl, lowercycloalkyl, loweralkylcycloalkyl, loweralkenyl, lower-haloalkenyl, lowerhydroxyalkenyl, loweralkynyl, lowerhalo-alkynyl, benzylamino, phenyl, loweralkylphenyl, loweralkoxy-loweralkyl, substituted phenyl, 2-methylfuran, di(Cl-C4)-alkylamino(Cl-C~)alkyl~ adamantyl or Rl and R2 taken together form a 5- or 6-membered heterocyclic moiety, Generally speaking, the process of thls invention comprises reacting an ester of adenosine-5'-carboxylic acid, or an acld addition salt of an ester of adenosine-5'-carboxylic ac d with an appropriate amine of the formula _,Rl or HNN ~ Rl .
in the presence of an appropriate alcohol.
15It is preferred that the ester or ester salt be suspended in a suitable alcohol such as methanol, ethanol, isopropanolJetc. and the amine is added to the alcohol suspension. The reaction proceeds best at temperatures above 70; however, it is preferred to reflux the reaction r~ 20 for a suitable length of time, ~ ~or at least 16 hours and usually for 16 to 18 hours. It is to be under- `
stood, however, that the reaction can be carried out for periods longer than 18 hours.
The amide is then recovered simply by, for exampleg ~.
concentrating the reaction to dryness and taking the residue .. ~ -
-2-` " . .
' ,. .
. , . ;' . .. ': .' ', . ` ~
1~38Z6~S
up in a minimum volume of water. The amide can then be recrystallized from water, if desired.
It is preferred to react the ester or ester salt with an excess of the appropriate amine. While an excess of amine is preferred, the ra~io of reactants should be at least 1:1 in the case of the ester plus the amine and at least 1:2 in the case of the ester salt and the amine.
It will be understood by those skilled in the art `- -that the particular amine, in the ester or the alcohol, détermines the final amide. While a number of esters can be used in the process of this invention, it is preerred e~hy J ~ enc~i nC ~ C'~r~'y ``
r~ to employ methyl adenosine-5'-carboxylate or late or a salt thereof~
In the preferred embodiment, e~hyl adenosine-S'- `
carboxylate hydrochloride i9 employed.
The process is represented by the following reaction scheme:
NH2 NH2 `;
N~
O+ HN 1 alcohol ~ Rl`N
RO ~ ~ R2 '. ~ I . ~, ~
OH-OH H
(or a salt thereof) :'`
' ,. .
. , . ;' . .. ': .' ', . ` ~
1~38Z6~S
up in a minimum volume of water. The amide can then be recrystallized from water, if desired.
It is preferred to react the ester or ester salt with an excess of the appropriate amine. While an excess of amine is preferred, the ra~io of reactants should be at least 1:1 in the case of the ester plus the amine and at least 1:2 in the case of the ester salt and the amine.
It will be understood by those skilled in the art `- -that the particular amine, in the ester or the alcohol, détermines the final amide. While a number of esters can be used in the process of this invention, it is preerred e~hy J ~ enc~i nC ~ C'~r~'y ``
r~ to employ methyl adenosine-5'-carboxylate or late or a salt thereof~
In the preferred embodiment, e~hyl adenosine-S'- `
carboxylate hydrochloride i9 employed.
The process is represented by the following reaction scheme:
NH2 NH2 `;
N~
O+ HN 1 alcohol ~ Rl`N
RO ~ ~ R2 '. ~ I . ~, ~
OH-OH H
(or a salt thereof) :'`
- 3- :
~ ~ 2 ~g ~ .
wherein Rl and R2 a.re 3.S deEined above and R is a.n a.liphatic or araliphatic group.
The preferred process ~ represented by the follow-ing reaction scheme:
NH2~HC~ NH2 ~ ROH ~ HN~ 1> ~ ~ _ ~
O NC .
CH3CH~OC l R2~ ~I ff H
0~1 ~1 The esters can be prepared by, for example, the method of German Patent No. 2,034,784. The acld addition salts of the esters are prepared by methods well known in : `
the art The amides can also be converted to their a.cid addition salt by reacting the amide with an appropriate ac~d in an appropriate solvent such as ethanol~ methanol, iso-propanol, etc.
The ollowing examples urther illustrate the .
15 present invention: :
Example 1 .:
Preparation of Ethyl-5'-(Adenosine Carboxyla~e) _ Hydrochloride Thionyl chloride (5 ml.) was added dropwise ~o a stirred suspension of adenosine-5'-carboxylic acid (5.62 g. ~.
1 ~ 8 2 ~ 5 0.02 mole) in absolute ethanol (400 ml.) at 0C. After the addition was complete, the mixture was stirred for 25 minutes.
The cooling bath was removed and the mixture stirred for 24 hours at room temperature. The mixture was cooled in ice-water and filtered to yield 6.7 g. of the desired product.
Recrystallization from absolute ethanol gave the product, m.p. 174 dec; ~726 -22.
~ ;;... .. .
. , .
' . .
"` .
-4a- -:, '` ':
:
`
, .. .... .
~8269~
Analysis Calcd- for C12H15N55 ~ICl C~
Cl, 10.27; N, 20.26 Found: C, 41.91; H, 4.91;
Cl, 10.07; N, 19.81 Example 2 Preparation of Aden ine-5'- rN-allyl)carboxamide7 To 150 ml. of absolute e~hanol were added 26 g. of ethyl-5'-(adenosine carboxylate)hydrochloride. To this mix-ture was added 35 mi. of allyl amine. The reaction was re-fluxed overn;ght (17-18 hours). The resulting amber colored ` `
solution was concentrated to dryness under pressure. The ~`residue was dissolved in water whereupon a solid rapidly crystallized. The solid was collected on a filter and washed with cold water to yield 23 g. of productJ m.p. 135-137, resolidified at 137 and remelts at 223-224. The product was dissol~ed in boiling water, treated with darco, iltered twice and allowed to crystallize. The solid was collected on a funnel, washed well with water and dried in vacuo at 84 overnight to yield 21.05 g. of product, m.p. 224-225. NMR
and TLC confirmed the identity of the product.
. . .
Example 3 Preparation of Adenosine-5'- ~N-cyclopropyl)carboxamid~7 To 60 ml. of absolute ethanol were added 5.5 g. of ethyl-5'-(adenosine carboxylate~hydrochloride. To the alcohol 2S mixture was added 10 ml. of c~clopropylamine. The mixture was `
heated to gentle reflux~ refluxed for 24 hours and cooled to room temperature whereupon a solid crystallized. The reaction mixture was concentrated to a solid residue under reduced .
.
~ ~ ~ 2 ~ ~
pressure. The residue was taken up in ice-wa~er whereupon a solid crystallized. The solid was collected on a filter and washed with ice-water to yield the 4.9 g, of crude product, m.p, 247-249. The crude product was dissolved in 200 ml. of hot water~ and the hot solution was treated with darco and filtered twice. The solution was cooled in `
an ice bath and the product was collected on a filter, washed with cold water, dried over night in vacuo at 84 to yield
~ ~ 2 ~g ~ .
wherein Rl and R2 a.re 3.S deEined above and R is a.n a.liphatic or araliphatic group.
The preferred process ~ represented by the follow-ing reaction scheme:
NH2~HC~ NH2 ~ ROH ~ HN~ 1> ~ ~ _ ~
O NC .
CH3CH~OC l R2~ ~I ff H
0~1 ~1 The esters can be prepared by, for example, the method of German Patent No. 2,034,784. The acld addition salts of the esters are prepared by methods well known in : `
the art The amides can also be converted to their a.cid addition salt by reacting the amide with an appropriate ac~d in an appropriate solvent such as ethanol~ methanol, iso-propanol, etc.
The ollowing examples urther illustrate the .
15 present invention: :
Example 1 .:
Preparation of Ethyl-5'-(Adenosine Carboxyla~e) _ Hydrochloride Thionyl chloride (5 ml.) was added dropwise ~o a stirred suspension of adenosine-5'-carboxylic acid (5.62 g. ~.
1 ~ 8 2 ~ 5 0.02 mole) in absolute ethanol (400 ml.) at 0C. After the addition was complete, the mixture was stirred for 25 minutes.
The cooling bath was removed and the mixture stirred for 24 hours at room temperature. The mixture was cooled in ice-water and filtered to yield 6.7 g. of the desired product.
Recrystallization from absolute ethanol gave the product, m.p. 174 dec; ~726 -22.
~ ;;... .. .
. , .
' . .
"` .
-4a- -:, '` ':
:
`
, .. .... .
~8269~
Analysis Calcd- for C12H15N55 ~ICl C~
Cl, 10.27; N, 20.26 Found: C, 41.91; H, 4.91;
Cl, 10.07; N, 19.81 Example 2 Preparation of Aden ine-5'- rN-allyl)carboxamide7 To 150 ml. of absolute e~hanol were added 26 g. of ethyl-5'-(adenosine carboxylate)hydrochloride. To this mix-ture was added 35 mi. of allyl amine. The reaction was re-fluxed overn;ght (17-18 hours). The resulting amber colored ` `
solution was concentrated to dryness under pressure. The ~`residue was dissolved in water whereupon a solid rapidly crystallized. The solid was collected on a filter and washed with cold water to yield 23 g. of productJ m.p. 135-137, resolidified at 137 and remelts at 223-224. The product was dissol~ed in boiling water, treated with darco, iltered twice and allowed to crystallize. The solid was collected on a funnel, washed well with water and dried in vacuo at 84 overnight to yield 21.05 g. of product, m.p. 224-225. NMR
and TLC confirmed the identity of the product.
. . .
Example 3 Preparation of Adenosine-5'- ~N-cyclopropyl)carboxamid~7 To 60 ml. of absolute ethanol were added 5.5 g. of ethyl-5'-(adenosine carboxylate~hydrochloride. To the alcohol 2S mixture was added 10 ml. of c~clopropylamine. The mixture was `
heated to gentle reflux~ refluxed for 24 hours and cooled to room temperature whereupon a solid crystallized. The reaction mixture was concentrated to a solid residue under reduced .
.
~ ~ ~ 2 ~ ~
pressure. The residue was taken up in ice-wa~er whereupon a solid crystallized. The solid was collected on a filter and washed with ice-water to yield the 4.9 g, of crude product, m.p, 247-249. The crude product was dissolved in 200 ml. of hot water~ and the hot solution was treated with darco and filtered twice. The solution was cooled in `
an ice bath and the product was collected on a filter, washed with cold water, dried over night in vacuo at 84 to yield
4.3 g. of the pure product, m.p. 252.5-253. NMR was consis-tent with the proposed structure.
Example 4 Preparation of Adenosine-5'- rN-isopropyl~carboxamid~
Ten grams of ethyl-5'-(adenosine carboxylate)hydro-chloride were added to 125 ml. of ethanol. To the ethanol mixture was added 25 ml. of isopropylamine. The reac~ion was heated at 50 for about 18 hours in a Parr shaker. An additional 25 ml. of isopropylamine was added and the reac-tion was heated at 70 for 24 hours. The reaction was then ~orked up following the procedure o~ Example 2 to yield 6.28 g. of product, m.p, 2040205. NMR confirmed the identity of the product.
Example 5 Preparation of Adenosine-5'- ~N-propargyl~carboxamid~7 To 120 ml. of absolute ethanol were added 10 g. of ~S ethyl-5'-~adenosine carboxylate)hydrochloride~ Propargyl amine (15 ml.) was added and the mixture refluxed for approximately 18 hours. The resulting reddish solution wa~
Z6~5 concentrated to dryness under reduced pressure. The residue was dissolved in a min~mum of cold water whereupon a solid qoon crystallized. The solid was chilled and collected on a filter to yield 7.7 g, of crude product, m.p~ 100. The ~5 crude product was dissolved in approximately 100 ml. of boil-ing water~ treated with darco and filtered. The reaction was then cooled in an ice bath. The solid was collected on `
a filter, washed with cold water and dried in a vacuum oven at 65 over the weekend to yield 6.49 g. of product, m.p.
118-121. NMR confirmed the identity of the product.
Example 6 Preparation of N-~-Hydroxyethyl)adenosine-5'-Carboxamide Ethyl adenosine-5'-carboxylate, hydrochloride (10 g.) was added to a solution of 20 ml. of ethanol amine in 150 ml.
of absolute ethanol. The reaction was refluxed overnight, concentrated to a solid residue under reduced pressure, and the residue taken up in a minimum of water and basified with NaHC03. The solution was reconcentrated to dryness and ex-tracted twice with hot absoluteethanol. Th~ filtrates were combined, heated to boiling and cooled to room temperature whereupon a solid slowly formed. The solid was recrystalliæed rom 450 ml. of ethanol whereupon the 4.75 g. of the product formed very slowly, m.p, l99-Z00. ~MR con~irmed the identity o~ the product.
.
Example 4 Preparation of Adenosine-5'- rN-isopropyl~carboxamid~
Ten grams of ethyl-5'-(adenosine carboxylate)hydro-chloride were added to 125 ml. of ethanol. To the ethanol mixture was added 25 ml. of isopropylamine. The reac~ion was heated at 50 for about 18 hours in a Parr shaker. An additional 25 ml. of isopropylamine was added and the reac-tion was heated at 70 for 24 hours. The reaction was then ~orked up following the procedure o~ Example 2 to yield 6.28 g. of product, m.p, 2040205. NMR confirmed the identity of the product.
Example 5 Preparation of Adenosine-5'- ~N-propargyl~carboxamid~7 To 120 ml. of absolute ethanol were added 10 g. of ~S ethyl-5'-~adenosine carboxylate)hydrochloride~ Propargyl amine (15 ml.) was added and the mixture refluxed for approximately 18 hours. The resulting reddish solution wa~
Z6~5 concentrated to dryness under reduced pressure. The residue was dissolved in a min~mum of cold water whereupon a solid qoon crystallized. The solid was chilled and collected on a filter to yield 7.7 g, of crude product, m.p~ 100. The ~5 crude product was dissolved in approximately 100 ml. of boil-ing water~ treated with darco and filtered. The reaction was then cooled in an ice bath. The solid was collected on `
a filter, washed with cold water and dried in a vacuum oven at 65 over the weekend to yield 6.49 g. of product, m.p.
118-121. NMR confirmed the identity of the product.
Example 6 Preparation of N-~-Hydroxyethyl)adenosine-5'-Carboxamide Ethyl adenosine-5'-carboxylate, hydrochloride (10 g.) was added to a solution of 20 ml. of ethanol amine in 150 ml.
of absolute ethanol. The reaction was refluxed overnight, concentrated to a solid residue under reduced pressure, and the residue taken up in a minimum of water and basified with NaHC03. The solution was reconcentrated to dryness and ex-tracted twice with hot absoluteethanol. Th~ filtrates were combined, heated to boiling and cooled to room temperature whereupon a solid slowly formed. The solid was recrystalliæed rom 450 ml. of ethanol whereupon the 4.75 g. of the product formed very slowly, m.p, l99-Z00. ~MR con~irmed the identity o~ the product.
.
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing an adenosine-5'-carbox-amide of the formula wherein R2 is loweralkynyl, comprising the steps of reacting an ester of adenosine-5'-carboxylic acid, or an acid addition salt thereof of the formula wherein R is an aliphatic or araliphatic group, with an amine of the formula wherein R2 is as defined above, in the presence of a suitable alcohol and recovering the amide from the reaction mixture.
2. The process of claim 1 wherein the alcohol is a lower aliphatic alcohol.
3. The process of claim 2 wherein the ester or ester salt is suspended in the alcohol and the amine is added thereto.
4. The process of claim 1, 2 or 3 wherein the reaction mixture is heated to a temperature of at least 70°
for at least 16 hours.
for at least 16 hours.
5. The process of claim 1, 2 or 3 wherein the reaction mixture is refluxed for a period of at least 16 hours.
6. A process for preparing an adenosine-5'-carbox-amide of the formula wherein R2 is propargyl, comprising the steps of: reacting a lower alkyl ester of adenosine-5'-carboxylic acid or an acid addition salt thereof with an amine of the formula: R2NH2 wherein R2 is as defined above, in a lower aliphatic alcohol and recovering the amide from the reaction mixture.
7. The process of claim 6 wherein the alcohol is ethanol and the ester is ethyl adenosine-5'-carboxylate.
8. The process of claim 6 wherein the alcohol is ethanol and the ester is methyl adenosine-5'-carboxylate.
9. The process or claim 6 wherein the alcohol is ethanol and the ester is ethyl adenosine-5'-carboxylate, hydro-chloride.
10. The process of claim 7, 8 or 9 wherein the reaction mixture is refluxed for a period of at least 16 hours and the amide is recovered from the reaction mixture by con-centrating the reaction to dryness, dissolving the residue in a minimum volume of water and recovering the resulting crystallized amide therefrom.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24277972A | 1972-04-10 | 1972-04-10 | |
| US242,779 | 1972-04-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1082695A true CA1082695A (en) | 1980-07-29 |
Family
ID=22916155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA164,578A Expired CA1082695A (en) | 1972-04-10 | 1973-02-26 | Process for preparing adenosine-5'-carboxamides |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS4913200A (en) |
| CA (1) | CA1082695A (en) |
| CH (1) | CH565175A5 (en) |
| DE (1) | DE2317770A1 (en) |
| FR (1) | FR2179886B1 (en) |
| GB (1) | GB1399670A (en) |
| ZA (1) | ZA731380B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7737126B2 (en) | 2004-05-24 | 2010-06-15 | Glaxo Group Limited | Purine derivative |
| US7985740B2 (en) | 2005-07-19 | 2011-07-26 | Glaxo Group Limited | Purine derivatives as agonists of the adenosine A2A receptor |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU198950B (en) * | 1986-12-15 | 1989-12-28 | Sandoz Ag | Process for producing new furanuronic acid derivatives and pharmaceutical compositions comprising such compounds |
| TW528755B (en) | 1996-12-24 | 2003-04-21 | Glaxo Group Ltd | 2-(purin-9-yl)-tetrahydrofuran-3,4-diol derivatives |
| YU44900A (en) | 1998-01-31 | 2003-01-31 | Glaxo Group Limited | 2-(purin-9-yl)-tetrahydrofuran-3,4-diol derivatives |
| US6495528B1 (en) | 1998-06-23 | 2002-12-17 | Smithkline Beecham Corporation | 2-(Purin -9-yl)-tetrahydrofuran-3,4-diol derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2034785A1 (en) * | 1970-07-14 | 1972-01-20 | Boehnnger Mannheim GmbH, 6800 Mann heim Waldhof | Adenosine 5 carboxylic acid derivatives |
-
1973
- 1973-02-26 CA CA164,578A patent/CA1082695A/en not_active Expired
- 1973-02-27 ZA ZA731380A patent/ZA731380B/en unknown
- 1973-03-29 GB GB1521473A patent/GB1399670A/en not_active Expired
- 1973-04-02 JP JP48036829A patent/JPS4913200A/ja active Pending
- 1973-04-09 DE DE2317770A patent/DE2317770A1/en active Pending
- 1973-04-10 FR FR7312779A patent/FR2179886B1/fr not_active Expired
- 1973-04-10 CH CH514273A patent/CH565175A5/xx not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7737126B2 (en) | 2004-05-24 | 2010-06-15 | Glaxo Group Limited | Purine derivative |
| US7985740B2 (en) | 2005-07-19 | 2011-07-26 | Glaxo Group Limited | Purine derivatives as agonists of the adenosine A2A receptor |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2317770A1 (en) | 1973-10-18 |
| GB1399670A (en) | 1975-07-02 |
| ZA731380B (en) | 1973-11-28 |
| FR2179886A1 (en) | 1973-11-23 |
| JPS4913200A (en) | 1974-02-05 |
| FR2179886B1 (en) | 1978-04-21 |
| CH565175A5 (en) | 1975-08-15 |
| AU5286573A (en) | 1974-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5610292A (en) | Process for producing 2,2'-o-cyclonucleosides nucleosides, and analogs thereof | |
| CA1082695A (en) | Process for preparing adenosine-5'-carboxamides | |
| CA1102794A (en) | Production of 2,6-diaminonebularines | |
| US3721664A (en) | Preparation of 5-cytosine nucleosides | |
| DD284024A5 (en) | PROCESS FOR THE PRODUCTION OF O HOCH 2 DEEP, 2'-ANHYDRO-1- (BETA-D-ARABINOFURANOSYL) THYMINE | |
| US5262531A (en) | Process for preparing 2'-deoxy-β-adenosine | |
| US3049536A (en) | Method for producing inosine | |
| US5532349A (en) | Process for producing 1-(2'-deoxy-β-D-erythro-pentofuranosyl)-5-trifluoromethyluracil derivatives | |
| US3058992A (en) | Intermediates for the preparation of | |
| US3853946A (en) | Process for the preparation of aminomethylene malononitrile | |
| US3277092A (en) | 5, 6-substituted dihydro-5-fluoropyrimidines | |
| US3287365A (en) | Novel dihydro-s-triazines and method of preparation | |
| EP0062068B1 (en) | N-phthalidyl-5-fluorouracil derivatives | |
| US5536824A (en) | Organosulfonyl salts of 2,3'-O-cyclocytidine | |
| DE1943428C3 (en) | Process for the preparation of pyrimidine and 6-azauracilnueleosides | |
| US3742015A (en) | Process for the preparation of aminomethylene malononitrile | |
| JPS633875B2 (en) | ||
| US4249006A (en) | Method of producing 5-fluorouracil derivatives | |
| US4279836A (en) | Hydroxamic acid derivative and method of preparing metoclopramide using same | |
| US4125728A (en) | Method for preparing 2,3,7,8-tetraazaspiro[4,4]nona-2,7-diene | |
| JPS5946511B2 (en) | 1-(N-hydroxyalkylcarbamoyl)-5-fluorouracils and their production method | |
| DE68922900T2 (en) | Process for the preparation of 2'-deoxy-beta-adenosine. | |
| US4065454A (en) | 1,3-Didesoxy-1,3-[N,N'-(1',2',3',4'-tetrahydro-1',4'-dioxo)-phthalazino]-inositol compounds | |
| SU511008A3 (en) | The method of obtaining 3- / dialkylaminoethyl / -4-alkyl7-carboethoxymethoxycoumarin | |
| CA1190234A (en) | Synthesis for (e)-2-(4-hydroxy-3-methyl-2-butenyl)- 1h-isoindole-1,3(2h)-dione |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |