# US 2025/0084102 A1 · Process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives

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- Number: US 2025/0084102 A1
- Document ID: US20250084102A1
- Status: Published application
- Kind: A1
- Application number: 18/797,280
- Filed: 2024-08-07
- Published: 2025-03-13
- Earliest claimed: 2017-09-22
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Jean-Michel ADAM; Serena Maria FANTASIA; Daniel Vincent FISHLOCK; Fabienne HOFFMANN-EMERY; Gerard MOINE; Christophe PFLEGER; Christian MOESSNER
- Web page: https://patentgrep.com/patent/US20250084102A1

## CPC

- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- B01J 23/44: Palladium
- B01J 23/755: Nickel
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

The present invention relates to a process for the preparation of 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one derivatives useful as pharmaceutically active compounds.

## Claims

### Claim at position 1

1-22. (canceled)

### Claim 23

A compound of formula (III):
wherein X is selected from an alkyl, aryl sulfonate, fluorinated alkyl, fluorinated aryl sulfonate and halide.

### Claim 24 (depends on 23)

The compound of claim 23, wherein X is selected from the group consisting of pTolSO3—, CH3SO3—, phenyl-SO3—, CF3SO3—, nonaflate, Cl, Br, and I.

### Claim 25 (depends on 23)

The compound of claim 23, wherein X is pTol-SO3—.

### Claim 26 (depends on 23)

The compound of claim 23, wherein X is CH3SO3—.

### Claim 27 (depends on 23)

The compound of claim 23, wherein X is CF3SO3—.

### Claim 28 (depends on 23)

The compound of claim 23, wherein X is phenyl-SO3—.

### Claim 29 (depends on 23)

The compound of claim 23, wherein X is Cl.

### Claim 30 (depends on 23)

The compound of claim 23, wherein the compound is prepared by a process which comprises
reacting a compound of formula (IV)
with
tosyl chloride when X is pTol-SO3—,
methanesulfonyl chloride when X is CH3SO3—,
triflyl chloride when X is CF3SO3—, or
phenylsulfonylchloride when X is phenyl-SO3—,
in the presence of a base;
or
POCl3 when X is Cl,
POBr3 when X is Br, or
Ph3PI2 or POCl3 followed by NaI or CuI, when X is I.

### Claim 31 (depends on 30)

The compound of claim 30, wherein the base is an organic base or basic alkali metal salts.

### Claim 32 (depends on 30)

The compound of claim 30, wherein the base is nitrogen-containing heterocycle, tertiary amine or basic alkali metal salts.

### Claim 33 (depends on 32)

The compound of claim 32, wherein the base is a tertiary amine.

### Claim 34

A compound of formula (IV):

### Claim 35 (depends on 34)

The compound of claim 34, wherein the compound is prepared by a process which comprises:
reacting a compound of formula (VII)
with a compound of formula (VIII)
or a salt thereof for the preparation of the compound of formula (VI);
reducing the compound of formula (VI) to provide the compound of formula (V); and
reacting a compound of formula (V) with di-tert-butyl malonate for the preparation of the compound of formula (IV).

### Claim 36 (depends on 35)

The compound of claim 35, wherein the salt of the compound of formula (VIII) is an oxalate salt.

### Claim 37 (depends on 35)

The compound of claim 35, wherein reducing the compound of formula (VI) comprises reacting said compound with a transition metal hydrogenation catalyst to obtain the compound of formula (V).

### Claim 38 (depends on 37)

The compound of claim 37, wherein the transition metal hydrogenation catalyst is selected from the group consisting of a Raney catalyst, Pd/C, Pd(OH)2/C, Au/TiO2, Rh/C, Ru/Al2O3, Ir/CaCO3, Pt—V/C, Pt/C and combinations thereof.

### Claim 39 (depends on 38)

The compound of claim 38, wherein the transition metal hydrogenation catalyst is Pt—V/C.

### Claim 40 (depends on 39)

The compound of claim 39, wherein the transition metal hydrogenation catalyst is Pt 1% and V 2% on activated carbon.

### Claim 41 (depends on 35)

The compound of claim 35, wherein reacting a compound of formula (V) with di-tert-butyl malonate is carried out in the presence of xylene, dichlorobenzene, toluene or anisole.

### Claim 42 (depends on 41)

The compound of claim 41, wherein said process is carried out in the presence of anisole.