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 2427269ノート

反応式

HRID 2427269 の反応式
[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]

参加物

6

反応物 4

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

生成物 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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

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).

後処理

  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%)

出典と根拠

ORDレコード
ord-12cce91ce4794ae98b40405062889bf3
出典データセット
uspto-grants-2011_06
特許番号
US07968587B2

反応ノート

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