The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl) NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl); S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl), comprising:
(a) reacting a compound having the structure:

##STR00002##

with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl) NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl); S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl), comprising:
(a) reacting a compound having the structure:

##STR00002##

with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl)NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl),
comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without subsutitution; and
R.sub.1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), NH-(alkyl), N(alkyl).sub.2, NH-(alkenyl), NH-(alkynyl)NH-(aryl), NH-(heteroaryl), O-(alkyl), O-(alkenyl), O-(alkynyl), O-(aryl), O-(heteroaryl), S-(alkyl), S-(alkenyl), S-(alkynyl), S-(aryl), or S-(heteroaryl),
comprising:
(a) reacting a compound having the structure: ##STR00002##
with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: ##STR00003##
and
(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: ##STR00004##

Tertiary amine catalysts having isocyanate reactive groups that are capable of forming thermally stable covalent bonds able to withstand temperatures up to 120 C. are disclosed. These catalyst can be used to produce polyurethane foam having the following desirable characteristics: a) very low chemical emissions over a wide range of environmental conditions and isocyanate indexes (e.g. indexes as low as 65 but higher than 60) while meeting all physical property requirements; b) sufficient hydrolytic stability to maintain the catalyst covalently bound to foam without leaching of tertiary amine catalyst when foam is exposed to water or aqueous solutions even at temperatures higher than ambient (temperature range 25 C. to 90 C.); and c) stable contact interface between the polyurethane polymer and other polymers (for example polycarbonate) with minimal migration of tertiary amine catalyst from polyurethane polymer to other polymers yielding no noticeable polymer deterioration at the point of contact even under conditions of heat and humidity.

Organic isocyanates are converted to ureas by heating in the presence of certain cobalt, magnesium, chromium and lanthanide series organometallic catalysts. The process requires no water or other reactants. The process is particularly useful for removing small quantities of monoisocyanates from a solvent stream recovered from a polyisocyanate manufacturing process. The urea compounds in some instances can be recycled back into the polyisocyanate manufacturing process and reacted with polyisocyanate compounds to form biurets.

Organic isocyanates are converted to ureas by heating in the presence of certain cobalt, magnesium, chromium and lanthanide series organometallic catalysts. The process requires no water or other reactants. The process is particularly useful for removing small quantities of monoisocyanates from a solvent stream recovered from a polyisocyanate manufacturing process. The urea compounds in some instances can be recycled back into the polyisocyanate manufacturing process and reacted with polyisocyanate compounds to form biurets.

A novel solid drug form of N-(2,6-bis(1-methylethyl)phenyl)-N-((1-(4-(dimethylamino)phenyl)cyclopentyl)methyl)urea hydrochloride (also referred to ATR-101) suitable for oral dosing, and to compositions, methods and kits relating thereto. ATR-101 has particular utility in the treatment of, for example, aberrant adrenocortical cellular activity, including adrenocortical carcinoma (ACC), congenital adrenal hyperplasia (CAH) and Cushing's syndrome.

The present invention is directed to a process for preparing amides or polyamides by replacing isocyanate starting materials of a catalyzed thermal reaction with aromatic carbamates. Through the catalyzed thermal process involving a non-isocyanate precursor of the present invention, efficiency for producing amides or polyamides can be significantly improved, and the impure side products produced from a side reaction of isocyanate can be greatly curtailed. Hence, amides or polyamides of high purity and yield can be achieved. The invention also relates to a process for preparing aromatic carbamates, the new non-isocyanate precursors for amides or polyamides.

A novel solid drug form of N-(2,6-bis(1-methylethyl)phenyl)-N-((1-(4-(dimethylamino)phenyl)cyclopentyl)methyl)urea hydrochloride (also referred to ATR-101) suitable for oral dosing, and to compositions, methods and kits relating thereto. ATR-101 has particular utility in the treatment of, for example, aberrant adrenocortical cellular activity, including adrenocortical carcinoma (ACC), congenital adrenal hyperplasia (CAH) and Cushing's syndrome.