2369-13-3Relevant articles and documents
The kinetics and mechanisms of aromatic nucleophilic substitution reactions in liquid ammonia
Ji, Pengju,Atherton, John H.,Page, Michael I.
scheme or table, p. 3286 - 3295 (2011/07/07)
The rates of aromatic nucleophilic substitution reactions in liquid ammonia are much faster than those in protic solvents indicating that liquid ammonia behaves like a typical dipolar aprotic solvent in its solvent effects on organic reactions. Nitrofluorobenzenes (NFBs) readily undergo solvolysis in liquid ammonia and 2-nitrofluorobenzene is about 30 times more reactive than the 4-substituted isomer. Oxygen nucleophiles, such as alkoxide and phenoxide ions, readily displace fluorine of 4-NFB in liquid ammonia to give the corresponding substitution product with little or no competing solvolysis product. Using the pKa of the substituted phenols in liquid ammonia, the Bronsted βnuc for the reaction of 4-NFB with para-substituted phenoxides is 0.91, indicative of the removal of most of the negative charge on the oxygen anion and complete bond formation in the transition state and therefore suggests that the decomposition of the Meisenheimer σ-intermediate is rate limiting. The aminolysis of 4-NFB occurs without general base catalysis by the amine and the second-order rate constants generate a Bronsted βnuc of 0.36 using either the pKa of aminium ion in acetonitrile or in water, which is also interpreted in terms of rate limiting breakdown of the Meisenheimer σ-intermediate. Nitrobenzene and diazene are formed as unusual products from the reaction between sodium azide and 4-NFB, which may be due to the initially formed 4-nitroazidobenzene decomposing to give a nitrene intermediate, which may then give diazene or be trapped by ammonia to give the unstable hydrazine which then yields nitrobenzene.
MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
-
Page/Page column 56, (2010/06/11)
Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette ('ABC') transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ('CFTR'). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
BROADSPECTRUM SUBSTITUTED BENZIMIDAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
-
Page/Page column 28-30, (2008/06/13)
The present invention concerns the compounds having the formula (I), wherein N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aRl0b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6alkanediyl-C(=O)-, -NR8-C1-6alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=O)2 ; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4alkyl)aminoC(=O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6alkanediyl-C(=O)-, C1-6 alkanediyl-C(=S)- or C1-6alkanediyl-S(=O)2-; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6 alkyl, optionally substituted amino--C1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6 alkyloxy-carbonylamino or amino; and in case _A- is other than C1-6alkanediyl then R6 may also be C1-6alkyl, Het1C1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; R5 and _A-R6 taken together with the nitrogen atom to which they are attached may also form Het1 or Het2, R12 , is H, - NH2, _NR5AR6, - C1-6alkyl or alkyl-W-R14 , wherein said alkyl is optionally substituted with halogen, hydroxy, aryl, heteroaryl, Het1, Het2, or amino wherein said amino is optionally mono- or di-substituted with C1-4alkyl and R13 is H, C1-6-alkyl, optionally substituted by aryl, Het1, Het2, hydroxy, halogen, amino whereby the amino group may be optionally be mono- or di-substituted with C1-4alkyl.