The present invention provides compounds of Formula (I):

##STR00001##

wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

The invention relates to a method of synthesizing methyl (Z)-3-[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl] amino]phenylmethylene)-oxindole-6-carboxylate of formula (1), known under the generic name of intedanib or nintedanib. The present method comprises a) a reaction of methyl oxindole-6-carboxylate with acetic anhydride at a temperature of 130-140 C., providing methyl 1-acetyl-oxindole-6-carboxylate; b) a reaction of methyl 1-acetyl-oxindole-6-carboxylate of with trimethyl orthobenzoate and acetic anhydride in the presence of toluene, providing methyl (E)-1-acetyl-3-(methoxyphenylmethylene)-oxindole-6-carboxylate; c) a reaction (E)-1-acetyl-3-(methoxyphenylmethylene)-oxindole-6-carboxylate with N-(4-aminophenyl)-N,4-dimethyl-1-piperazine acetamide and subsequently with an alkali hydroxide or alkali alkoxide in methanol or ethanol without isolation of the intermediate, providing methyl (Z)-3-[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl] amino]phenylmethylene)-oxindole-6-carboxylate, wherein the reaction is conducted at a temperature of 50 to 100 C. (1). ##STR00001##

An iridium (III) complex compound with cyclic quinoxaline-fused dibenzosuberene ligand is shown in General Formula (1),

##STR00001## wherein m is 1 or 2, n is 1 or 2, and m+n is 3; A is a bridging atom represented by General Formula (2) or General Formula (3),

##STR00002## wherein R.sub.1 is a hydrogen atom, alkyl or tert-butyl group, R.sub.2 to R.sub.14 are independently selected from the group consisting of hydrogen atom, halogen atom, cyano group, alkyl group, cycloalkyl group, aryl group, alkoxy group, amino group, thioalkyl group, silyl group and alkenyl group.

An iridium (III) complex compound with cyclic quinoxaline-fused dibenzosuberene ligand is shown in General Formula (1),

##STR00001## wherein m is 1 or 2, n is 1 or 2, and m+n is 3; A is a bridging atom represented by General Formula (2) or General Formula (3),

##STR00002## wherein R.sub.1 is a hydrogen atom, alkyl or tert-butyl group, R.sub.2 to R.sub.14 are independently selected from the group consisting of hydrogen atom, halogen atom, cyano group, alkyl group, cycloalkyl group, aryl group, alkoxy group, amino group, thioalkyl group, silyl group and alkenyl group.

The present invention provides compounds of Formula (I): ##STR00001##
wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

The present invention provides compounds of Formula (I): ##STR00001##
wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

The disclosure features methods of analyzing a fluid extracted from a reservoir, the methods including introducing a first composition featuring a first complexing agent into a reservoir at a first location, extracting a fluid from the reservoir at a second location different from the first location, combining the fluid with a second composition featuring a concentration of a lanthanide ion to form a third composition featuring a concentration of a complex formed by the first complexing agent and the lanthanide ion, exposing a quantity of the complex to electromagnetic radiation for a first time period ending at a time to, detecting fluorescence emission from the quantity of the complex for a second time period starting at a time t.sub.1>t.sub.0, where t.sub.1?t.sub.0 is greater than 2 microseconds, and determining information about a fluid flow path between the first location and the second location.

Disclosed herein are compounds and methods of treating diseases and/or conditions associated with FGFR inhibition.

The present disclosure provides methods of producing a compound of structural formula (I): (I) or a pharmaceutically acceptable salt thereof.

##STR00001##

Provided are compounds of Formula I: ##STR00001##
or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, X and m are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.