(R)-8-(2-chloro-1-methylethyl)-8-azaspiro[4.5]decane-7,9-dione → 8-{(1R)-2-[4-(2,5-Difluorophenyl)piperazin-1-yl]-1-methylethyl}-8-azaspiro[4.5]decane-7,9-dione

HRID 49022

反応式

HRID 49022 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.Cl[CH2:16][C@H:17]([N:19]1[C:28](=[O:29])[CH2:27][C:22]2([CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:21][C:20]1=[O:30])[CH3:18]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:18][C@H:17]([N:19]2[C:28](=[O:29])[CH2:27][C:22]3([CH2:26][CH2:25][CH2:24][CH2:23]3)[CH2:21][C:20]2=[O:30])[CH3:16])[CH2:13][CH2:14]1

参加物

3

反応物 2

HCID 11322499(R)-8-(2-chloro-1-methylethyl)-8-azaspiro[4.5]decane-7,9-dioneHCID 185452811-(2,5-Difluorophenyl)piperazine

生成物 1

HCID 542086998-{(1R)-2-[4-(2,5-Difluorophenyl)piperazin-1-yl]-1-methylethyl}-8-azaspiro[4.5]decane-7,9-dione収率 66%

反応条件

温度
160 °C

実験手順

A mixture of 1-(2,5-difluorophenyl)piperazine (20 mg, 0.10 mmol) and (R)-8-(2-chloro-1-methylethyl)-8-azaspiro[4.5]decane-7,9-dione (20 mg, 0.082 mmol) was heated with stirring at 160° C. for 5 hours. The residue was purified by preparative HPLC [reverse phase column (C18 HC), water/methanol (70:30) with 0.1% TFA to water/methanol (40:60) with 0.1% TFA gradient, UV detection at λ254 nm or λ215 nm], giving (after removal of the solvent) the title compound as a pale yellow oil (21.5 mg, 0.05 mmol, 66%): ESI-MS m/z 406 (MH+).

後処理

  1. temperaturewas heated
  2. customThe residue was purified by preparative HPLC [reverse phase column (C18 HC), water/methanol (70:30) with 0.1% TFA to water/methanol (40:60) with 0.1% TFA gradient, UV detection at λ254 nm or λ215 nm]
  3. customgiving (

出典と根拠

ORDレコード
ord-d8accf4fd2044fddb8131a0bb01c10ba
出典データセット
uspto-grants-2004_03
特許番号
US06706716B2

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