# US 10,501,422 B2 · Processes for the resolution of benzodiazepin-2-one and benzoazepin-2-one derivatives

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,501,422 B2
- Document ID: US10501422B2
- Status: Granted
- Kind: B2
- Application number: 16/188,954
- Filed: 2018-11-13
- Published: 2019-06-13
- Granted: 2019-12-10
- Earliest claimed: 2017-11-13
- Assignees: Enanta Pharmaceuticals, Inc.
- Applicants: Enanta Pharmaceuticals, Inc.
- Inventors: Andrew Hague; Matthew Ronsheim
- Web page: https://patentgrep.com/patent/US10501422B2

## CPC

- C07D 243/26: Preparation from compounds already containing the benzodiazepine skeleton
- C07B 57/00: Separation of optically-active compounds
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention relates to processes and intermediates useful in the preparation of biologically active molecules, especially in the synthesis of Respiratory Syncytial Virus (RSV) inhibitors. The present invention also relates to processes and intermediates for the preparation of compounds of Formula (I-0) and Formula (I):

## Claims

### Claim 1

A process for the preparation of a compound of Formula (I):
wherein X is N or CH;
said process comprising:
(a) reacting a compound of Formula (I′),
with a compound of Formula (III),
wherein R is optionally substituted phenyl, to yield a compound of Formula (IV),
provided that said reaction takes place in the absence of an aromatic aldehyde; and
(b) treating the compound of Formula (IV) with a base to provide the compound of Formula (I).

### Claim 2 (depends on 1)

The process of claim 1, wherein R is

### Claim 3 (depends on 1)

The process of claim 1, wherein X is N.

### Claim 4 (depends on 1)

The process of claim 1, wherein X is CH.

### Claim 5 (depends on 1)

The process of claim 1, wherein step (a) is carried out in a solvent selected from acetonitrile, methanol, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, 1,2-dimethoxyethane, dichloromethane, 1,4-dioxane, toluene, anisole, ethanol, acetone, N,N-dimethylformamide, N,N-dimethylacetamide, pyridine and isopropyl acetate or a combination of two or more thereof.

### Claim 6 (depends on 5)

The process of claim 5, wherein step (a) is carried out in a solvent selected from tetrahydrofuran and 1,4-dioxane.

### Claim 7 (depends on 1)

The process of claim 1, wherein in step (b), the base is sodium hydroxide, potassium carbonate, ammonium hydroxide, potassium phosphate tribasic or sodium carbonate.

### Claim 8 (depends on 7)

The process of claim 7, wherein the base is 1N sodium hydroxide, 5 wt % potassium carbonate, 28-30% ammonium hydroxide, 10 wt % potassium phosphate tribasic or 5 wt % sodium carbonate.

### Claim 9 (depends on 1)

The process of claim 1, wherein in step (a) the compound of Formula (I′) is in a mixture with its enantiomer.

### Claim 10 (depends on 9)

The process of claim 9, wherein the mixture is a racemic mixture.

### Claim 11

A process for the preparation of a compound of Formula (I-0):
wherein X is N or CH; R1 is halogen, CN or optionally substituted C1-C3 alkyl; and n is 0, 1, 2 or 3;
said process comprising:
(a) reacting a compound of Formula (I′-0),
with a compound of Formula (III),
wherein R is optionally substituted phenyl, to yield a compound of Formula (IV-0),
provided that said reaction takes place in the absence of an aromatic aldehyde; and
(b) treating a compound of Formula (IV-0) with a base to provide a compound of Formula (I-0).

### Claim 12 (depends on 11)

The process of claim 11, wherein R is

### Claim 13 (depends on 11)

The process of claim 11, wherein X is N.

### Claim 14 (depends on 11)

The process of claim 11, wherein X is CH.

### Claim 15 (depends on 11)

The process of claim 11, wherein step (a) is carried out in a solvent selected from acetonitrile, methanol, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, 1,2-dimethoxyethane, dichloromethane, 1,4-dioxane, toluene, anisole, ethanol, acetone, N,N-dimethylformamide, N,N-dimethylacetamide, pyridine and isopropyl acetate, or a combination of two or more thereof.

### Claim 16 (depends on 15)

The process of claim 15, wherein step (a) is carried out in a solvent selected from tetrahydrofuran and 1,4-dioxane.

### Claim 17 (depends on 11)

The process of claim 11, wherein in step (b), the base is sodium hydroxide, potassium carbonate, ammonium hydroxide, potassium phosphate tribasic or sodium carbonate.

### Claim 18 (depends on 17)

The process of claim 17, wherein the base is 1N sodium hydroxide, 5 wt % potassium carbonate, 28-30% ammonium hydroxide, 10 wt % potassium phosphate tribasic or 5 wt % sodium carbonate.

### Claim 19 (depends on 11)

The process of claim 11, wherein in step (a) the compound of Formula (I′-0) is present in a mixture with its enantiomer.

### Claim 20 (depends on 19)

The process of claim 19, wherein the mixture is a racemic mixture.

### Claim 21 (depends on 1)

The process of claim 1 wherein step (a) is conducted at a temperature of about 20° C. to about 45° C.

### Claim 22 (depends on 11)

The process of claim 11 wherein step (a) is conducted at a temperature of about 20° C. to about 45° C.