- 5-Pyrimidylboronic acid and 2-methoxy-5-pyrimidylboronic acid: New heteroarylpyrimidine derivatives via Suzuki cross-coupling reactions
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5-Pyrimidylboronic acid 2 and 2-methoxy-5-pyrimidylboronic acid 4 have been synthesised by lithium-halogen exchange reactions on 5-bromopyrimidine and 2-methoxy-5-bromopyrimidine, respectively, followed by reaction with triisopropylborate. Suzuki cross-coupling reactions of 2 and 4 with heteroaryl halides [Na2CO3, Pd(PPh3)2Cl 2, 1,4-dioxane, 95°C] yield heteroarylpyrimidines (heteroaryl = thienyl, quinolyl and pyrimidyl). Two-fold reaction of 2 with 4,6-dichloropyrimidine 12 gave 4,6-bis(5-pyrimidyl)pyrimidine 8 (56% yield). Reaction of 4,6-dichloro-pyrimidine with 2-methoxy-5-pyridylboronic acid gave 4,6-bis(2-methoxy-5-pyridyl)pyrimidine 14 (84% yield). Conversion of 14 into 4,6-bis(2-chloro-5-pyridyl)pyrimidine 15 (63% yield) followed by two-fold Suzuki reaction with 4-tert-butylbenzeneboronic acid gave the penta-arylene derivative 4,6-bis(2-(4-ferf-butyl)phenyl-5-pyridyl]pyrimidine 16 (16% yield). Analogous reaction of 12 with 2-methoxy-3-pyridylboronic acid 17 gave 4,6-bis(2-methoxy-3- pyridyl)pyrimidine 18 (64% yield). The X-ray crystal structures of compound 2.05H2O and compound 18 are reported. The two hydroxyl H atoms in 2 have the usual exo-endo orientation. However, unlike most arylboronic acids, molecule 2 does not form a centrosymmetric hydrogen-bonded dimer. In molecule 18, the pyridine rings form dihedral angles of 39.9° and 22.8° with the central pyrimidine ring.
- Saygili, Nezire,Batsanov, Andrei S.,Bryce, Martin R.
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- Improved synthesis of azaheteroarylboronic acids using tris-trimethylsilylborate under mild conditions
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A new family of azaheteroarylboronic acids was synthesized with good yields (70% to 75%). The proposed strategy utilizes an improved transmetalation reaction from Grignard azine reagents and tris-trimethylsilylborate, little used until now.
- Matondo, Hubert,Souirti, Souad,Baboulene, Michel
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- PHOSPHATIDYLINOSITOL 3 KINASE INHIBITORS
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Provided are compounds according to Formula (I), or stereoisomer, prodrug, polymorph, or pharmaceutically acceptable salt forms thereof, wherein X, Y, R1, R6 , R7, and R8 are as defined, which compounds are effective inhibitors of PI3-kinase and/or other medically and clinically relevant kinases. Also provided are pharmaceutical compositions and methods of using the compounds and compositions as PB -kinase and kinase inhibitors. More particularly, the compounds of the invention provide treatments and therapeutics for human diseases regulated by, or associated with, the activity of, PI3-kinases and/or protein kinases, or mutant or variant forms thereof.
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Page/Page column 133-134
(2010/01/12)
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- Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
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The present invention relates to a method of treating disorders by administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I): wherein R1-R8 are as described herein, R4 being aryl or heteroaryl.
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Page/Page column 17
(2008/06/13)
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- BENZOXAZOCINES AND THEIR THERAPEUTIC USE AS MONOAMINE REUPTAKE INHIBITORS
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Compounds having therapeutic utility are of general formula (1) wherein R, is H, C 1-C6 alkyl optionally substituted with F or C3-C6 cycloalkyl or C2-C4 alkenyl; A is O, CH2 or S(O)n where n is 0-2; one of W, X, Y and Z is N, CH or CR3 and the others are CH; R2 is C5-C6 heteroaryl, C5-C10 cycloalkyl or cycloalkenyl optionally containing one or more heteroatoms selected from O, N and S(O)n where n is 0-2, and optionally substituted with R3; or a phenyl group optionally substituted in one or more positions with one or more substituents independently selected from halogen, CN, CF3, C1-C6 alkyl and OR1, or the phenyl group is fused to a five or six membered ring which may be carbocyclic, heterocyclic (containing 1-2 heteroatoms selected from O, N and S), aromatic or heteroaromatic (containing 1-2 heteroatoms selected from O and N); R3 is selected from halogen; CF3; CN; OR5; SO2N(R5)2; COR5; CO2R5; CON(R5)2; NR1,COR4; NR1SO2R4; NR1CO2R4; NR1,CON(R5)2; OC1-C6 alkyl substituted with R3; C1-C6 alkyl optionally substituted with unsubstituted R3; C3-C6 cycloalkyl optionally substituted with unsubstituted R3; C2-Cs alkenyl optionally substituted with unsubstituted R3; C2-Cs alkynyl optionally substituted with unsubstituted R3; aryl optionally substituted with unsubstituted R3; and five or six membered aromatic heterocycles containing 1-4 heteroatoms selected from N and O; R4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl and heteroaryl; and R5 is H, C1-C6 alkyl; C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl or heteroaryl and is the same as or different to another R5; or a pharmaceutically acceptable salt thereof.
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Page/Page column 16
(2010/02/14)
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- An improved protocol for the preparation of 3-pyridyl- and some arylboronic acids
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3-Pyridylboronic acid was prepared in high yield and bulk quantity from 3-bromopyridine via a protocol of lithium-halogen exchange and "in situ quench". This technique was further studied and evaluated on other aryl halides in the preparation of arylboronic acids.
- Li, Wenjie,Nelson, Dorian P.,Jensen, Mark S.,Hoerrner, R. Scott,Cai, Dongwei,Larsen, Robert D.,Reider, Paul J.
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p. 5394 - 5397
(2007/10/03)
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