Cesium carbonate → (S)-{7-cyano-4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl}-carbamic acid isopropyl ester

HRID 2427269노트

반응식

HRID 2427269 반응식
[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].Br[CH2:23][C:24]1[C:25]([N:30]2[C:38](=[O:39])[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]2=[O:40])=[N:26][CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C1C=CC=CN=1)C>CS(C)=O>[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[N:11]([CH2:23][C:24]3[C:25]([N:30]4[C:31](=[O:40])[C:32]5[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=5)[C:38]4=[O:39])=[N:26][CH:27]=[CH:28][CH:29]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 218852-DimethylaminopyridineHCID 20792249HCID 20792249, 화합물HCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

생성물 1

HCID 59242747(S)-{7-cyano-4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-pyridin-3-ylmethyl]-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl}-carbamic acid isopropyl ester

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

Dissolve (S)-(7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (20 g, 70.59 mmoles; ee>98%, 2nd isomer on Chiracel OJ, 0.2% DMEA in Hexane/EtOH [80:20]) in dimethyl sulfoxide (160 mL) and add 2-(3-bromomethyl-pyridin-2-yl)-isoindole-1,3-dione (29.8 g, 84.71 mmol). Stir the mixture until a clear solution is obtained. Add cesium carbonate (46.4 g, 141.18 mmoles) and dimethylaminopyridine (875.5 mg, 7.06 mmol) in one portion. Stir the resulting mixture at 22/24° C. for 2 h. Add the mixture onto water (1.4 L). Stir the resulting suspension for 30 min and filter. Wash the resulting cake with water (100 ml). Dissolve the isolated wet solid in dichloromethane (750 mL) and separate the organic layer. Wash the organic layer with brine and evaporate the organic solvent. Purify the resulting material by silica gel chromatography, eluting with hexanes/acetone/CH2Cl2 (3/1/1) to obtain 24 g (58%). MS (m/z): 520 (M+1).

후처리

  1. customis obtained
  2. stirringStir the resulting mixture at 22/24° C. for 2 h
  3. additionAdd the mixture onto water (1.4 L)
  4. stirringStir the resulting suspension for 30 min
  5. filtrationfilter
  6. washWash the resulting cake with water (100 ml)
  7. dissolutionDissolve the isolated wet solid in dichloromethane (750 mL)
  8. customseparate the organic layer
  9. washWash the organic layer with brine
  10. customevaporate the organic solvent
  11. customPurify the resulting material by silica gel chromatography
  12. washeluting with hexanes/acetone/CH2Cl2 (3/1/1)
  13. customto obtain 24 g (58%)

출처 및 근거

ORD 기록
ord-12cce91ce4794ae98b40405062889bf3
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07968587B2

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