Some content of this application is unavailable at the moment.
If this situation persist, please contact us atFeedback&Contact
1. (WO2018138500) PROCESS FOR PREPARING PURINE DERIVATIVES
Latest bibliographic data on file with the International Bureau    Submit observation

Pub. No.: WO/2018/138500 International Application No.: PCT/GB2018/050208
Publication Date: 02.08.2018 International Filing Date: 25.01.2018
IPC:
C07D 473/16 (2006.01) ,A61P 35/00 (2006.01) ,A61K 31/52 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
473
Heterocyclic compounds containing purine ring systems
02
with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6
16
two nitrogen atoms
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
33
Heterocyclic compounds
395
having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
495
having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
505
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
519
ortho- or peri-condensed with heterocyclic rings
52
Purines, e.g. adenine
Applicants:
CYCLACEL LIMITED [GB/GB]; New Bridge Street House 30-34 New Bridge Street London Greater London EC4V 6BJ, GB
Inventors:
SKEAD, Ben; GB
WESTWOOD, Robert; GB
LONDESBROUGH, Derek; GB
NORTHERN, Julian; GB
ATHERTON, Chris; GB
Agent:
CLYDE-WATSON, Zoe; GB
Priority Data:
1701318.626.01.2017GB
1701319.426.01.2017GB
1701397.027.01.2017GB
1701398.827.01.2017GB
Title (EN) PROCESS FOR PREPARING PURINE DERIVATIVES
(FR) PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE PURINE
Abstract:
(EN) The present invention relates to a process for preparing a compound of formula [I], said process comprising the steps of: formula [II]+formula [III]−>formula [I] (i) forming a reaction mixture comprising (a) a compound of formula [II], (b) a compound of formula [III] and (c) 1,2-propanediol or polyethylene glycol, or a mixture thereof, and optionally (d) a base; (ii) heating said reaction mixture to a temperature of at least about 150°C to form a compound of formula [I]; (iii) isolating said compound of formula [I]; and (iv) optionally converting said compound of formula [I] into salt form; wherein: R1 and R2 are each independently H, alkyl or haloalkyl; R3 and R4 are each independently H, alkyl, haloalkyl or aryl; R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups; R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and formula (A) where one of X, Y and Z is N and the remainder are CR9; R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H. Further aspects of the invention relate to a highly diastereoselective process for the preparation of compounds of formula [III], a process for preparing intermediates of formula [II], and other intermediates useful in the synthesis of compounds of formula [I], and to a process for preparing the crystalline tartrate salt and free base of compounds of formula [I].
(FR) La présente invention concerne un procédé de préparation d'un composé de formule [I], ledit procédé comprenant les étapes consistant à : formule [II] + formule [III] −> formule [I] (i) former un mélange réactionnel comprenant (a) un composé de formule [II], (b) un composé de formule [III] et (c) du 1,2-propanédiol ou du polyéthylène glycol, ou un mélange de ceux-ci, et éventuellement (d) une base ; (ii) chauffer ledit mélange réactionnel à une température d'au moins environ 150 °C pour former un composé de formule [I] ; (iii) isoler ledit composé de formule [I] ; et (iv) convertir éventuellement ledit composé de formule [I] en forme de sel ; R1 et R2 étant chacun indépendamment H, un alkyle ou un haloalkyle ; R3 et R4 étant chacun indépendamment H, un alkyle, un haloalkyle ou un aryle ; R5 représente un alkyle, un alcényle, un cycloalkyle ou un cycloalkyle-alkyle, chacun de ceux-ci pouvant être éventuellement substitué par un ou plusieurs groupes OH ; R6 est choisi parmi cyclopropylamino, cyclopropylméthylamino, cyclobutylamino, cyclobutylméthylamino et la formule (A) où un parmi X, Y et Z représente N et le reste étant CR9 ; R7, R8 et chaque R9 représente indépendamment H, un alkyle ou un haloalkyle, au moins l'un de R7, R8 et R9 étant différent de H. Selon d'autres aspects, l'invention concerne un procédé hautement diastéréosélectif pour la préparation de composés de formule [III], un procédé de préparation d'intermédiaires de formule [II], et d'autres intermédiaires utiles dans la synthèse de composés de formule [I], et un procédé de préparation du sel de tartrate cristallin et de la base libre de composés de formule [I].
front page image
Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)