US 8501730

US Patent 8501730, titled "Process for preparing benzazepine compounds or salts thereof," was issued to Otsuka Pharmaceutical Co Ltd.. The patent was filed on May 17, 2012, and granted on August 6, 2013. The inventors listed are Yasuhiro Torisawa, Kaoru Abe, Yasuaki Muguruma, Shigekazu Fujita, Hidenori Ogawa, Naoto Utsumi, and Masahiro Miyake.

Abstract Overview:
The invention provides a method for preparing benzazepine compounds of formula (1) and intermediate benzoic acid compounds of formula (4) with high yield and purity on an industrial scale. These compounds are valuable as intermediates for creating pharmaceutically active 2,3,4,5-tetrahydro-1H-1-benzazepine compounds, which act as vasopressin antagonists.

Plain-Language Overview of Independent Claims:

• Claim 1: This claim covers a process for making a specific type of benzazepine compound (formula 1) or its salts. The process involves reacting a benzazepine compound (formula 2) with an amide compound (formula 3) in the presence of a carbonylating agent. In these compounds, X1 and X2 are halogen atoms, and R1 and R2 are lower alkyl groups.
• Claim 2: This claim describes a process for producing a benzoic acid compound (formula 4) or its salts. This process involves reacting an amide compound (formula 11) with an oxalyl halide compound (formula 19), where X6 and X7 are independently halogen atoms. R1 and R2 are lower alkyl groups.
• Claim 3: This claim outlines a process for obtaining a benzoic acid compound (formula 4) or its salts by oxidizing an amide compound (formula 12) or its salts. X3 is a halogen atom, and R1 and R2 are lower alkyl groups.
• Claim 4: This claim details a process for producing a benzoic acid compound (formula 4) or its salts through the hydrolysis of an amide compound (formula 13) or its salts. X3 is a halogen atom, and R1 and R2 are lower alkyl groups.
• Claim 5: This claim covers a process for producing a benzoic acid compound (formula 4) or its salts by oxidizing an amide compound (formula 14) or its salts. R1 and R2 are lower alkyl groups.
• Claim 6: This claim describes a process for producing a 2,3,4,5-tetrahydro-1H-1-benzazepine compound (formula 10) or its salts. This is achieved by reducing a benzazepine compound (formula 1) or its salt using a hydrogenating agent. The crucial aspect is that the hydrogenating agent is used in a specific amount: between 0.1 to 1 mole per 1 mole of compound (1). R1 and R2 are lower alkyl groups, and X1 is a halogen atom.

Litigation Information (CAFC 2026 Dockets):
As of May 21, 2026, US Patent 8501730 has been involved in litigation at the Court of Appeals for the Federal Circuit. In the nonprecedential case Otsuka Pharmaceutical Co. v. Lupin Ltd. (No. 24-2297), the Federal Circuit affirmed a lower court's judgment that Lupin's tolvaptan ANDA process does not infringe US Patent 8501730. Additionally, the asserted method claims of the patent were found invalid as obvious over a 1999 synthesis paper by Kondo.