US4910307A
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Process for preparing purines
Assignee: Beecham Group PLC
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Filing: 1988-10-20
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Granted: 1990-03-20
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Expires: 2008-10-20
Abstract
Abstract A process for the preparation of compounds of formula (I), and pharmaceutically acceptable salts thereof: ##STR1## wherein R 1 is hydrogen or CH 2 OH; R 2 is hydrogen or, (when R 1 is hydrogen), hydroxy or CH 2 OH; R 3 is CH 2 OH or, (when R 1 and R 2 are both hydrogen), CH(OH)CH 2 OH; R 4 is hydrogen, hydroxy, amino or OR 5 wherein R 5 is C 1-6 alkyl, phenyl or phenyl C 1-2 alkyl either of which phenyl moieties may be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups; and in which any OH groups in R 1 , R 2 and/or R 3 may be in the form of O-acyl, phosphate, cyclic acetal or cyclic carbonate derivatives thereof; which process comprises the reaction of a compound of formula (II): ##STR2## wherein R 4 ' is R 4 or a group or atom convertible thereto and R x is amino or protected amino; with a compound of formula (III): R.sub.3 'CHR.sub.2 'CHR.sub.1 'Q (III) wherein Q is a leaving group and R 1 ', R 2 ' and R 3 ' are R 1 , R 2 and R 3 respectively or R 1 , R 2 and/or R 3 wherein the OH group(s) is/are in protected form; and thereafter converting R 4 ' when other than R 4 , to an R 4 moiety or converting R 4 ' when R 4 to other R 4 ; if necessary converting R 1 ', R 2 ' or R 3 ' to R 1 , R 1 and R 3 respectively and optionally forming a pharmaceutically acceptable salt, O-acyl, phosphate, cyclic acetal or cyclic carbonate derivative thereof.
Inventors
- 👤 Paul G. Wyatt
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 10:42
CPC Classifications
C; C07; C07D; C07D473/00; C07D473/02; C07D473/18; C07D473/16; C07D473/26; C07D473/32
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
324 words
A process for the preparation of compounds of formula (I), and pharmaceutically acceptable salts thereof: ##STR9## wherein R 1 is hydrogen or CH 2 OH; R 2 is hydrogen or, (when R 1 is hydrogen), hydroxy or CH 2 OH; R 3 is CH 2 OH or, (when R 1 and R 2 are both hydrogen), CH(OH)CH 2 OH; R 4 is hydrogen, hydroxy, amino or OR 5 wherein R 5 is C 1-6 alkyl, phenyl or phenyl C 1-2 alkyl either of which phenyl moieties may be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups; and in which any OH groups in R 1 , R 2 and/or R 3 may be in the form of, C 1-7 alkanoyl and benzoyl optionally substituted by one or two C 1-4 alkyl, C 1-4 alkoxy, halogen or CF 3 groups, phosphate, --O--C(C 1-3 alkyl) 2 --O--, or --O--CO--O-- derivatives thereof; which process comprises the reaction of a compound of formula (II): ##STR10## wherein R 4 ' is R 4 or a group or atom convertible thereto and R x is amino or protected amino; with a compound of formula (III): R.sub.3 'CHR.sub.2 'CHR.sub.1 'Q (III) wherein Q is a leaving group and R 1 ', R 2 ' and R 3 ' are R 1 , R 2 and R 3 respectively, one or more of which may have a protected OH group; and thereafter treating R 4 ' in a conventional manner to convert R 4 ' to R 4 or, if R 4 ' is R 4 , to convert R 4 ' to another R 4 ; and, if necessary, treating R 1 ', R 2 ' or R 3 ' to form R 1 , R 2 and R 3 , respectively, and optionally forming a pharmaceutically acceptable salt, phosphate, carboxylic ester, --O--C(C 1-3 alkyl) 2 --O--, or --O--CO--O-- derivative thereof, according to conventional methods.
Claim 2
Dependent Claim
324 words
A process for the preparation of compounds of formula (I), and pharmaceutically acceptable salts thereof: ##STR9## wherein R 1 is hydrogen or CH 2 OH; R 2 is hydrogen or, (when R 1 is hydrogen), hydroxy or CH 2 OH; R 3 is CH 2 OH or, (when R 1 and R 2 are both hydrogen), CH(OH)CH 2 OH; R 4 is hydrogen, hydroxy, amino or OR 5 wherein R 5 is C 1-6 alkyl, phenyl or phenyl C 1-2 alkyl either of which phenyl moieties may be substituted by one or two halo, C 1-4 alkyl or C 1-4 alkoxy groups; and in which any OH groups in R 1 , R 2 and/or R 3 may be in the form of, C 1-7 alkanoyl and benzoyl optionally substituted by one or two C 1-4 alkyl, C 1-4 alkoxy, halogen or CF 3 groups, phosphate, --O--C(C 1-3 alkyl) 2 --O--, or --O--CO--O-- derivatives thereof; which process comprises the reaction of a compound of formula (II): ##STR10## wherein R 4 ' is R 4 or a group or atom convertible thereto and R x is amino or protected amino; with a compound of formula (III): R.sub.3 'CHR.sub.2 'CHR.sub.1 'Q (III) wherein Q is a leaving group and R 1 ', R 2 ' and R 3 ' are R 1 , R 2 and R 3 respectively, one or more of which may have a protected OH group; and thereafter treating R 4 ' in a conventional manner to convert R 4 ' to R 4 or, if R 4 ' is R 4 , to convert R 4 ' to another R 4 ; and, if necessary, treating R 1 ', R 2 ' or R 3 ' to form R 1 , R 2 and R 3 , respectively, and optionally forming a pharmaceutically acceptable salt, phosphate, carboxylic ester, --O--C(C 1-3 alkyl) 2 --O--, or --O--CO--O-- derivative thereof, according to conventional methods.
Claim 3
Dependent Claim
44 words
A process according to claim 1 for the preparation of a compound of formula (I) as defined in claim 1, wherein R 1 is hydrogen and R 2 and R 3 are both CH 2 OH, and derivatives thereof as defined in claim 1.
Claim 4
Dependent Claim
44 words
A process according to claim 1 for the preparation of a compound of formula (I) as defined in claim 1, wherein R 1 is hydrogen, R 2 is hydroxy and R 3 is CH 2 OH, and derivatives thereof as defined in claim 1.
Claim 5
Dependent Claim
46 words
A process according to claim 1 for the preparation of a compound of formula (I) as defined in claim 1, wherein R 1 is CH 2 OH, R 2 is hydrogen and R 3 is CH 2 OH, and derivatives thereof as defined in claim 1.
Claim 6
Dependent Claim
44 words
A process according to claim 1 for the preparation of a compound of formula (I) as defined in claim 1, wherein R 1 and R 2 are both hydrogen and R 3 is CH(OH)CH 2 OH, and derivatives thereof as defined in claim 1.
Claim 7
Dependent Claim
50 words
A process according to claim 1 for the preparation of a compound of formula I as defined in any one of claims 2 to 5 wherein OH groups in R 1 , R 2 , and/or R 3 are in the form of an acetate, hexanoate or benzoate derivative thereof.
Claim 8
Dependent Claim
50 words
A process according to claim 1 for the preparation of a compound of formula (I) which is: 9-(3-hydroxyprop-1-oxy)guanine, 9-(3-acetoxyprop-1-oxy)guanine, 9-(3-benzoyloxyprop-1-oxy)guanine, 2-amino-6-ethoxy-9-(3-hydroxyprop-1-oxy)purine, 9-(3-hydroxy-2-hydroxymethylprop-1-oxy)guanine, 9-(2,3-dihydroxyprop-1-oxy)guanine, 2-amino-9-(2,3-dihydroxyprop-1-oxy)purine, 9-(1,4-dihydroxybut-2-oxy)guanine, 2-amino-9-(1,4-dihydroxybut-2-oxy)purine, 2-amino-9-(3-hydroxyprop-1-oxy)purine, 9-(3-hexanoyloxyprop-1-oxy)guanine, 2-amino-9-(1,4-diacetoxybut-2-oxy)purine, 2-amino-9-(1,4-dibutyryloxybut-2-oxy)purine, (R)-9-(1,4-dihydroxybut-2-oxy)guanine, (S)-9-(1,4-dihydroxybut-2-oxy)guanine, 2-amino-9-(3-hydroxy-2-hydroxymethylprop-1-oxy)purine, 9-(3-acetoxy-2-acetoxymethylprop-1-oxy)-2-aminopurine, 2-amino-9-(3-propionyloxy-2-propionyloxymethylprop-1-oxy)purine, 2-amino-9-(3-benzoyloxy-2-benzoyloxymethylprop-1-oxy)purine, 2-amino-9-(3-hydroxy-2-hydroxymethylprop-1-oxy)-6-methoxypurine, 2,6-diamino-9-(3-hydroxy-2-hydroxymethylprop-1-oxy)purine, 9-(3-acetoxyprop-1-oxy)-2-aminopurine, 2-amino-9-(3-hexanoyloxyprop-1-oxy)purine, 2-amino-9-(3-benzoyloxyprop-1-oxy)purine, (S)-9-(1,4-diacetoxybut-2-oxy)guanine, 2-amino-9-(2,3-dihydroxyprop-1-oxy)-6-methoxypurine, (R)-9-(2,3-dihydroxyprop-1-oxy)guanine, 9-(3,4-dihydroxybut-1-oxy)guanine, 2-amino-9-(3,4-dihydroxybut-1-oxy)purine, (R)-2-amino-9-(2,3-dihydroxyprop-1-oxy)purine, (S)-9-(2,3-dihydroxyprop-1-oxy)guanine or (S)-2-amino-9-(2,3-dihydroxyprop-1-oxy)purine.
References Cited (Backward Citations)
US4701526A
Cited
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