Avacopan metabolite M1 → cis-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-formyl-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide

HRID 2273872Notes

Reaction equation

HRID 2273872 reaction equation
[CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][C:10]([C@H:13]3[C@@H:18]([C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([CH2:28][OH:29])=[C:24]([C:30]([F:33])([F:32])[F:31])[CH:23]=4)=[O:20])[CH2:17][CH2:16][CH2:15][N:14]3[C:34](=[O:43])[C:35]3[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=3[F:42])=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1>ClCCCl.ClCCl.O=[Mn]=O>[CH:1]1([NH:6][C:7]2[CH:8]=[CH:9][C:10]([C@H:13]3[C@@H:18]([C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([CH:28]=[O:29])=[C:24]([C:30]([F:32])([F:33])[F:31])[CH:23]=4)=[O:20])[CH2:17][CH2:16][CH2:15][N:14]3[C:34](=[O:43])[C:35]3[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=3[F:42])=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 1

HCID 58506551Avacopan metabolite M1

Product 1

HCID 58506541cis-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-formyl-3-(trifluoromethyl)phenyl]piperidine-3-carboxamideYield 31%

Reagents, catalysts & solvents 3

HCID 14801Manganese dioxideCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of cis-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methyl-benzoyl)-N-[4-(hydroxymethyl)-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide (130 mg, 0.22 mmol) in 1,2-dichloroethane (2 mL) was added MnO2 (380 mg, 4.4 mmol) at room temperature. The reaction mixture was stirred for 3 h and was then diluted with dichloromethane, filtered through a plug of SiO2, and the filtrate was concentrated under reduced pressure. The residue was purified by HPLC to get the desired compound (as a mixture of cis enantiomers) in 31% yield (40 mg). 1H NMR (400 MHz, CDCl3) δ 10.2 (bs, 1H), 8.12-6.88 (m, 10H), 3.82-3.04 (m, 4H), 2.88-1.40 (m, 18H). MS: (ES) m/z 596 (M+H+).

Workup

  1. filtrationfiltered through a plug of SiO2
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-f489b4b1a5db446cbacdcf730a1e6312
Source dataset
uspto-grants-2015_09
Patent number
US09126939B2

Reaction notes

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