1,1'-Carbonyldiimidazole → (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid

HRID 383969

반응식

HRID 383969 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:20]1[C@H:25]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:24](=[O:30])[NH:23][C@H:22]([CH:31]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32]2)[C:21]1=[O:40])[C:10](NC1C=CC=CC=1O)=[O:11].C(N1C=CN=C1)(N1C=CN=C1)=[O:42]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:20]1[C@H:25]([CH2:26][CH:27]([CH3:28])[CH3:29])[C:24](=[O:30])[NH:23][C@H:22]([CH:31]2[CH2:32][C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:39]2)[C:21]1=[O:40])[C:10]([OH:42])=[O:11]

참가 물질

4

반응물 2

HCID 682631,1'-CarbonyldiimidazoleHCID 11649656(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N-(2-hydroxyphenyl)ethanamide

생성물 1

HCID 68844874(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid수율 69%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N-(2-hydroxyphenyl)ethanamide (2.650 g) was stirred in dichloromethane (20 ml) and carbonyldiimidazole (1.178 g) was added. the mixture was left at room temperature for 16 hours then the solvent was removed under reduced pressure. The residue was then taken up in 1:1 acetone:water (v/v) (80 ml) and left at room temperature for 30 minutes. The bulk of the acetone was then removed under reduced pressure and the residue was partitioned between dichloromethane and 0.5M hydrochloric acid. The organic phase was separated (hydrophobic frit) and evaporated under reduced pressure. The crude product was purified (Biotage™ flash chromatography column, 90 g silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1) to afford (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid as a colourless solid 1.524 g as a mixture of epimers.

후처리

  1. customthe solvent was removed under reduced pressure
  2. waitwater (v/v) (80 ml) and left at room temperature for 30 minutes
  3. customThe bulk of the acetone was then removed under reduced pressure
  4. customthe residue was partitioned between dichloromethane and 0.5M hydrochloric acid
  5. customThe organic phase was separated (hydrophobic frit)
  6. customevaporated under reduced pressure
  7. customThe crude product was purified
  8. wash(Biotage™ flash chromatography column, 90 g silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1)

출처 및 근거

ORD 기록
ord-14ef7acde02f440d9ef8ebcb9e04bbfe
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367673B2

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