1,2-Dichloroethane → N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-N'-[(2S,3R)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]pentanediamide;formic acid

HRID 14331

반응식

HRID 14331 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:30])[CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])[C@H:7]([OH:21])[CH2:8][NH:9][C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=2)[CH2:12][CH2:11]1.[CH2:35](Cl)[CH2:36]Cl.[CH:39]1[CH:40]=C[C:42]2[N:47](O)N=[N:45][C:43]=2[CH:44]=1>CN(C=O)C>[N:47]12[CH2:36][CH2:35][CH:44]([CH2:39][CH2:40]1)[C@@H:43]([NH:45][C:27](=[O:29])[CH2:26][CH2:25][CH2:24][C:23]([NH:22][C@@H:6]([CH2:5][C:4]1[CH:31]=[C:32]([F:34])[CH:33]=[C:2]([F:1])[CH:3]=1)[C@H:7]([OH:21])[CH2:8][NH:9][C:10]1([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=3)[CH2:11][CH2:12]1)=[O:30])[CH2:42]2.[CH:27]([OH:29])=[O:28]

참가 물질

5

반응물 3

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 575126575-[((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)amino]-5-oxopentanoic Acid

생성물 1

HCID 86594205N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-N'-[(2S,3R)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]pentanediamide;formic acid수율 49.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
45 °C

실험 절차

To a solution of S-aminoquinuclidine (0.084 g, 0.421 mmol) TEA (0.294 ml, 2.11 mmol), and anhydrous DMF (2.5 ml) was added 5-[((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)amino]-5-oxopentanoic acid (0.200 g, 0.421 mmol), EDC (0.121 g, 0.632 mmol), HOBT (0.085 g, 0.632 mmol) under nitrogen, with stirring at 45° C. overnight. Reaction mixture was quenched with 10% sodium bicarbonate (aq.) then extracted with ethyl acetate then concentrated in vacuo, yielding product (0.065 g). Prep-HPLC yielded the product as its formate salt. (ES+: 583.3)

후처리

  1. customReaction mixture
  2. customwas quenched with 10% sodium bicarbonate (aq.)
  3. extractionthen extracted with ethyl acetate
  4. concentrationthen concentrated in vacuo

출처 및 근거

ORD 기록
ord-723305476ba042b995e91746ed80415c
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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