# US 2022/0033408 A1 · Process for preparing spiro derivatives

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- Number: US 2022/0033408 A1
- Document ID: US20220033408A1
- Status: Published application
- Kind: A1
- Application number: 17/502,653
- Filed: 2021-10-15
- Published: 2022-02-03
- Earliest claimed: 2017-10-10
- Assignees: Biogen, Inc.
- Applicants: Biogen Inc.
- Inventors: Gerard M. Giblin; David T. MacPherson; Osama Suleiman; Michael Williams; David R. Witty; Thierry Bonnaud; Richard Edwards
- Web page: https://patentgrep.com/patent/US20220033408A1

## CPC

- C07D 487/10: Spiro-condensed systems
- C07C 51/412: {by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part}
- C07C 215/28: and containing six-membered aromatic rings
- C07D 207/273: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D 207/277: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The invention relates to a novel process for preparing spiro derivatives, in particular 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, and to novel intermediates for use in said process along with processes for preparing said intermediates.

## Claims

### Claim 1

A compound which is (S)-1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidine-3-carboxylic acid (D6):

### Claim 2 (depends on 1)

A process of preparing the compound of D6 as defined in claim 1, from a compound which is (S)-1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidine-3-carboxylic acid (S)-phenylglycinol salt (D5):

### Claim 3

A process of preparing a compound which is (S) tert-Butyl(1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidin-3-yl)carbamate (D7):
which comprises:
(i) preparing a compound of D1:
from 1-methylpyrrolidin-2-one; followed by
(ii) preparing a compound of D4:
from a compound of D1; followed by
(iii) preparing a compound of D5:
from a compound of D4, followed by
(iv) preparing a compound of D6:
from a compound of D5; and followed by
(v) preparing a compound of D7:
from a compound of D6.

### Claim 4

A process of preparing a compound which is (S) tert-Butyl(1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidin-3-yl)carbamate (D7):
which comprises:
(a) preparing a compound of D2:
from 1-methylpyrrolidin-2-one; followed by
(b) preparing a compound of D3:
from a compound of D2: followed by
(c) preparing a compound of D4:
from a compound of D3, followed by
(iii) preparing a compound of D5:
from a compound of D4; followed by
(iv) preparing a compound of D6:
from a compound of D5; and followed by
(v) preparing a compound of D7:
from a compound of D6.

### Claim 5 (depends on 3, 4)

A process of preparing a compound which is 7-methyl-2-[4-methyl-6-[4-trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, i.e. a compound of formula (I):
which comprises:
steps (i) to (v) as defined in claim 3; or steps (a) to (c) followed by steps (iii) to (v) as defined in claim 4; followed by:
(vi) preparing a compound of D9:
from a compound of D7 and a compound of D8:
followed by
(vii) preparing a compound of D10:
from a compound of D9; followed by
(viii) preparing a compound of formula (I):
from a compound of D10.

### Claim 6

A process of preparing a compound which is D1:
from 1-methylpyrrolidin-2-one.

### Claim 7

A process of preparing a compound of D2:
from 1-methylpyrrolidin-2-one.

### Claim 8

A process of preparing a compound of D3:
from a compound of D2.

### Claim 9

A process of preparing a compound of D4:
from a compound of D3.

### Claim 10

A process of preparing a compound of D4:
from a compound of D1.

### Claim 11

A process of preparing a compound of D5:
from a compound of D4.

### Claim 12

A process of preparing a compound of D7:
from a compound of D6.

### Claim 13

A process of preparing a compound of D9:
from a compound of D7 and a compound of D8:

### Claim 14

A process of preparing a compound of D10
from a compound of D9.

### Claim 15

A process of preparing a compound of formula (I):
from a compound of D10.