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 2427269Notes

Reaction equation

HRID 2427269 reaction equation
[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]

Participants

6

Reactant 4

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

Product 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

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

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).

Workup

  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%)

Sources & evidence

ORD record
ord-12cce91ce4794ae98b40405062889bf3
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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