IE67294B1 - Process for the preparation of 2-acylamino-9-acyl-6-halopurine - Google Patents
Process for the preparation of 2-acylamino-9-acyl-6-halopurineInfo
- Publication number
- IE67294B1 IE67294B1 IE451790A IE451790A IE67294B1 IE 67294 B1 IE67294 B1 IE 67294B1 IE 451790 A IE451790 A IE 451790A IE 451790 A IE451790 A IE 451790A IE 67294 B1 IE67294 B1 IE 67294B1
- Authority
- IE
- Ireland
- Prior art keywords
- compound
- formula
- preparation
- acyl
- pyridine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 230000010933 acylation Effects 0.000 claims description 6
- 238000005917 acylation reaction Methods 0.000 claims description 6
- -1 carboxylic acid halide Chemical class 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003222 pyridines Chemical class 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Chemical group 0.000 claims description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 2
- QJWQYVJVCXMTJP-UHFFFAOYSA-N 4-pyridin-4-ylmorpholine Chemical compound C1COCCN1C1=CC=NC=C1 QJWQYVJVCXMTJP-UHFFFAOYSA-N 0.000 claims description 2
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XFUAHBGSAKYMNK-UHFFFAOYSA-N n-(9-acetyl-6-chloropurin-2-yl)acetamide Chemical compound CC(=O)NC1=NC(Cl)=C2N=CN(C(C)=O)C2=N1 XFUAHBGSAKYMNK-UHFFFAOYSA-N 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- FGWQRDGADJMULT-UHFFFAOYSA-N 4-(4-methylpiperidin-1-yl)pyridine Chemical compound C1CC(C)CCN1C1=CC=NC=C1 FGWQRDGADJMULT-UHFFFAOYSA-N 0.000 description 1
- VQDQISMDUHBUFF-UHFFFAOYSA-N 4-phenylbutanoyl chloride Chemical compound ClC(=O)CCCC1=CC=CC=C1 VQDQISMDUHBUFF-UHFFFAOYSA-N 0.000 description 1
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HTWWKYKIBSHDPC-UHFFFAOYSA-N decanoyl decanoate Chemical compound CCCCCCCCCC(=O)OC(=O)CCCCCCCCC HTWWKYKIBSHDPC-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- RZZCIBFHZYEENN-UHFFFAOYSA-N n-(6-chloro-7h-purin-2-yl)acetamide Chemical compound CC(=O)NC1=NC(Cl)=C2NC=NC2=N1 RZZCIBFHZYEENN-UHFFFAOYSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- RAFYDKXYXRZODZ-UHFFFAOYSA-N octanoyl octanoate Chemical compound CCCCCCCC(=O)OC(=O)CCCCCCC RAFYDKXYXRZODZ-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RIBFXMJCUYXJDZ-UHFFFAOYSA-N propanoyl bromide Chemical compound CCC(Br)=O RIBFXMJCUYXJDZ-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
2-Acylamino-9-acyl-6-halogeno-purine can be prepared by acylating 2-acylamino-6-halogeno-purine in the presence of a catalyst without the contaminating production of 2-diacylamino-9-acyl-6-chloro-purine.
Description
2-Acyl amino-9-acyl-6 -chloropurines are very widely utilizable intermediates in the pharmaceutical industry for nucleoside syntheses.
The preparation of 2-acetamido-9-acetyl-6-chloropurine by acetylation of 2-amino-6-chloropurine has already been described (Synthetic Procedures in Nucleic Acid Chemistry, Vol. 1, 1968, W.W. Zorbach and R.S. Tipson Ed., John Wiley & Sons, New York, 25 - 27) . In this case, the acetylation in position 9 of the purine ring is preferably carried out under reflux conditions. However, even after 5 to 10 minutes reaction time, 2-diacetamido9-acetyl-6-chloropurine is also formed as an impurity in addition to 2-acetamido-9-acetyl-6-chloropurine. The total yield of the two compounds is 75%.
Some experiments moreover show that under the abovemen tioned conditions at reflux temperatures of 135C to 140°C, not only are larger amounts of 2-diacetamido-9acetyl-6-chloropurine formed, but a replacement of chlorine by oxygen in position 6 of the purine ring additionally also takes place. These disadvantages particularly have an influence in the preparation of larger amounts of 2 -acetamido- 9 -acetyl- 6 - chloropur ine. On the production scale, longer heating and cooling times cannot be avoided, so that the high thermal loadings lead to strongly contaminated 2-acetamido-9-acetyl-6-chloropurine batches.
Surprisingly, it has now been found that by the use of a catalyst the purity of 2-acylamino-9-acyl-6-halopurine can be substantially improved in the preparation from 2acylamino- 6 -halopurine.
The invention thus relates to a process for the preparation of the compound of the formula I in which R1 and R2, which can be identical or different, are a straight-chain or branched alkanoyl group having 2 to 10 carbon atoms or an aralkanoyl group having 7 to 10 carbon atoms and X is fluorine, chlorine, bromine or iodine, by acylation of the compound of the formula II IX in which R1 and X have the abovementioned meaning, which comprises using pyridine or a pyridine derivative as the catalyst and carrying out the acylation at a temperature of between 10°C and 90°C.
The invention will now be described in detail in the following, in particular in its preferred embodiments.
The expression alkanoyl group having 2 to 10 carbon atoms is to be understood as meaning, for example, the radicals of the following acids: acetic acid, propionic acid, n-butyric acid, i-butyric acid, n-valeric acid, i-valeric acid, methylethylacetic acid, trimethylacetic acid, caproic acid, caprylic acid, capric acid, heptanoic acid and nonanoic acid. The expression aralkanoyl group having 7 to 10 carbon atoms means, for exasple, the radicals of the following compounds: benzoic acid, phenylacetic acid, phenylpropanoic acid, phenyl-n-butyric acid or phenyl-i-butyric acid.
The reaction, according to the invention, of 2-acylamino6-halopurine to give 2-acylamino-9-acyl-6-halopurine is carried out in the presence of an acylating agent, with V the aid of which the amino group in the 9-position of the compound of the formula IX can be substituted by a straight-chain or branched alkanoyl group having 2 to 10 carbon atoms or an aralkanoyl group having 7 to 10 carbon atoms. Acylating agents which can be used are carboxylic anhydrides, such as, for example, acetic anhydride, propionic anhydride, butyric anhydride, valeric anhydride, caprylic anhydride, capric anhydride or caproic anhydride. However, mixed anhydrides can also be employed. In addition, acylating agents which can also be used are carboxylic acid halides, such as acetyl chloride, propionyl chloride, phenylacetyl chloride, phenylbutanoyl chloride, benzoyl chloride, acetyl bromide, or propionyl bromide. The acylating agents can be dissolved in an inert solvent beforehand. Inert solvents which can be used are compounds such as, for example, dimethylacetamide, toluene, benzene or N-methylpyrrolidone.
-Acylamino-6-halopurine is mixed with the acylating agent and heated with the addition of a catalyst. The following compounds can be used as catalyst: pyridine, pyridine derivatives such as, for example, 4dimethylaminopyridine, 4- (4-methyl-1-piperidinyl)pyridine, 4-pyrrolidinopyridine, 4-morpholinopyridine or N-methylimidazole. Preferably, 4-dimethylaminopyridine is used. 'i The molar ratio of 2-acyl amino-6-halopurine to the acylating agent can be varied within a range from 1:1 to 1:40. The reaction is preferably carried out in a range from 1:5 to 1:30. The molar ratio of catalyst to 2acylamino-6-halopurine can vary within a range from 1:5 to 1:100. Preferably, a molar ratio of 1:35 to 1:80 is maintained.
The reaction temperature is between 10°C and 90°C, in particular between 20°C and 70°C. The reaction time is between 0.5 and 7 hours, in particular between 1 and 3 hours. The course of the reaction is determined by sample removal and quantitative analysis of the final product with the aid of known titration methods. After this, the mixture is stirred at temperatures between 0°C and 10°C for a. further 0.5 to 2 hours. After filtration, the compound of the formula I is obtained in high purity.
The sequence of the individual process steps can also be varied. A person skilled in the art does not find it difficult to find the optimum sequence for the reaction process.
The preparation of 2-acylamino-6-halopurines is carried out in a manner known per se by halogenation and acylation of purines (EP 0,203,685; D.J. Brown, Heterocyclic Compounds, 135-197, 1971; Bowles W.A. et al., J. Med. Chem., 471-480, 6, 1963).
In comparison to the route known hitherto for the preparation of 2-acylamino-9-acyl-6-halopurines, the process according to the invention opens up the advantage of obtaining the final product in high purity and yield. The catalysts used catalyze the acylation in position 9 of the purine ring, but not the formation of 2-diacylamino-9-acyl-6-halopurines. All process steps which are needed for the separation of the 2-diacylamino-9-acyl-6halopurine derivatives thus become unnecessary.
The example shown below is used to illustrate the invention further.
Example: 1.1 kg (5.2 mol) o£ 2-acetamido-6-chloropurine are suspended in 11 1 of acetic anhydride and 87.0 g (0.71 mol) of 4-dime thyl aminopyridine are added. The mixture is stirred at 50°C for two hours, then cooled and stirred at 0°C to 5°C for half an hour. The product is filtered off, washed with diisopropyl ether and dried in vacuo at 50°C. 1.16 kg of 2-acetamido-9-acetyl-6-chloropurine are obtained.
Yield: 88% of theory Purity: 99.1% (titration) ^H-NMR (in DMSO) : δ (ppm): 2.25 N-C-CH3 2.93 9-COCH3 8.93 8-H 11.06 HN-CO-C
Claims (8)
1. A process for the preparation of the compound of the formula I X in which R 1 and R 2 , which can be identical or 5 different, are a straight-chain or branched alkanoyl group having 2 to 10 carbon atoms or an aralkanoyl group having 7 to 10 carbon atoms and X is fluorine, chlorine, bromine or iodine, by acylation of the compound of the formula IZ 10 in which R 1 and X have the abovementioned meaning, which conqprises using pyridine or a pyridine derivative as the catalyst and carrying out the acylation at a temperature of between 10°C and 90°C. ; t 2. The process as claimed in claim 1, wherein carboxylic anhydride or carboxylic acid halide are used as the acylating agent. The process as claimed in claim 1, wherein
2. 4-dimethylaminopyridine, 4- (4-methyl-1-piper idinyl) 3. pyridine, 4-pyrrolidinopyridine, 4-morpholinopyridine or N-methylimidazole are used as the pyridine derivative. 4. The process as claimed in one or more of claims 1 to
3. 5 3, wherein the molar ratio of the compound of the formula II to acylating agent is in the range from 1:1 to 1:40. 5. The process as claimed in claim 4, wherein the molar ratio is in the range from 1:5 to 1:30. 10
4. 6. The process as claimed in one or more of claims 1 to 5, wherein the molar ratio of catalyst to the compound of the formula II is in the range from 1:5 to 1:100.
5. 7. The process as claimed in claim 6, wherein the molar 15 ratio is between 1:35 to 1:80.
6. 8. The process as claimed in claim 1, wherein the reaction temperature is between 20°C and 70°C.
7. 9. A process according to claim 1 for the preparation of a compound of the formula I given and defined 2 θ therein, substantially as hereinbefore described and exemplified.
8. 10. A compound of the formula I given and defined in claim 1, whenever prepared by a process claimed in a preceding claim.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3941658A DE3941658A1 (en) | 1989-12-16 | 1989-12-16 | METHOD FOR PRODUCING 2-ACYLAMINO-9-ACYL-6-HALOGEN PURIN |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE904517A1 IE904517A1 (en) | 1991-06-19 |
| IE67294B1 true IE67294B1 (en) | 1996-03-20 |
Family
ID=6395643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE451790A IE67294B1 (en) | 1989-12-16 | 1990-12-14 | Process for the preparation of 2-acylamino-9-acyl-6-halopurine |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0433845B1 (en) |
| JP (1) | JPH0692965A (en) |
| AT (1) | ATE120748T1 (en) |
| DE (2) | DE3941658A1 (en) |
| DK (1) | DK0433845T3 (en) |
| ES (1) | ES2071731T3 (en) |
| IE (1) | IE67294B1 (en) |
| PT (1) | PT96179B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9201961D0 (en) * | 1992-01-30 | 1992-03-18 | Smithkline Beecham Plc | Pharmaceuticals |
| JPH07133276A (en) * | 1993-09-17 | 1995-05-23 | Jiyuuzen Kagaku Kk | Production of 2-acetylamono-6-chloropurine |
| ES2287260T3 (en) * | 2001-04-05 | 2007-12-16 | Sumitomo Chemical Company, Limited | PROCEDURE TO PRODUCE 2,6-DIHALOGENOPURIN. |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR79681B (en) * | 1982-10-14 | 1984-10-31 | Wellcome Found | |
| EP0138683A3 (en) * | 1983-09-30 | 1988-01-20 | Merck & Co. Inc. | Purine derivatives, their application in anti-viral compositions |
-
1989
- 1989-12-16 DE DE3941658A patent/DE3941658A1/en not_active Withdrawn
-
1990
- 1990-12-11 DK DK90123792.5T patent/DK0433845T3/en active
- 1990-12-11 AT AT90123792T patent/ATE120748T1/en not_active IP Right Cessation
- 1990-12-11 DE DE59008852T patent/DE59008852D1/en not_active Expired - Fee Related
- 1990-12-11 ES ES90123792T patent/ES2071731T3/en not_active Expired - Lifetime
- 1990-12-11 EP EP90123792A patent/EP0433845B1/en not_active Expired - Lifetime
- 1990-12-13 PT PT96179A patent/PT96179B/en not_active IP Right Cessation
- 1990-12-14 IE IE451790A patent/IE67294B1/en not_active IP Right Cessation
- 1990-12-14 JP JP2419202A patent/JPH0692965A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0692965A (en) | 1994-04-05 |
| ATE120748T1 (en) | 1995-04-15 |
| IE904517A1 (en) | 1991-06-19 |
| PT96179B (en) | 1998-04-30 |
| EP0433845B1 (en) | 1995-04-05 |
| DE59008852D1 (en) | 1995-05-11 |
| EP0433845A1 (en) | 1991-06-26 |
| DE3941658A1 (en) | 1991-06-20 |
| ES2071731T3 (en) | 1995-07-01 |
| PT96179A (en) | 1991-09-30 |
| DK0433845T3 (en) | 1995-07-31 |
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