Cesium carbonate → HCID 44624002, compound

HRID 2274046Notes

Reaction equation

HRID 2274046 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]([CH2:14][C:15]([O:17]CC)=[O:16])[CH2:12][CH2:13][C:5]=3[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:27][C:28]1[CH:29]=[CH:30][C:31]([O:36][C:37]([F:40])([F:39])[F:38])=[C:32]([CH:35]=1)[C:33]#[N:34]>CN(C=O)C>[C:33]([C:32]1[CH:35]=[C:28]([CH:29]=[CH:30][C:31]=1[O:36][C:37]([F:38])([F:40])[F:39])[CH2:27][O:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]([CH2:14][C:15]([OH:17])=[O:16])[CH2:12][CH2:13][C:5]=3[C:4]=2[CH:3]=1)#[N:34]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 53345675Ethyl 2-(7-hydroxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetateHCID 67211302HCID 67211302, compound

Product 1

HCID 44624002HCID 44624002, compoundYield 24.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Ethyl 2-(7-hydroxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (0.100 g, 0.386 mmol) and cesium carbonate (0.138 g, 0.424 mmol) were dissolved in DMF (1.0 mL), stirred at room temperature for 10 min, followed by addition of 5-(chloromethyl)-2-(trifluoromethoxy)benzonitrile (0.100 g, 0.424 mmol) in DMF (0.300 mL) at 0° C. This mixture was stirred at room temperature for 3 h. The reaction mixture was quenched with water and extracted with ethylacetate (2×50 mL). The organic phase was washed with brine and concentrated. The residue was taken up in dioxane (4 mL) before aqueous 1 N LiOH (1.3 mL) was added. The mixture was stirred at room temperature for 2.5 h before it was quenched with water and acidified to pH 3 using aqueous 3 N HCl. The mixture was purified by HPLC to give the title compound (0.040 g). LCMS m/z=431.2 [M+H]+, 1H NMR (500 MHz, DMSO-d6) ppm 2.00-2.20 (m, 1H), 2.01-2.21 (m, 1H), 2.23-2.43 (m, 1H), 2.55-2.83 (m, 4H), 3.33-3.57 (m, 1H), 5.16 (s, 2H), 6.73 (dd, J=8.83, 2.52 Hz, 1H), 6.94 (s, 1H), 7.21 (d, J=8.83 Hz, 1H), 7.69 (dd, J=8.67, 1.42 Hz, 1H), 7.94 (dd, J=8.67, 2.05 Hz, 1H), 8.09 (s, 1H), 10.40 (s, 1H).

Workup

  1. stirringThis mixture was stirred at room temperature for 3 h
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with ethylacetate (2×50 mL)
  4. washThe organic phase was washed with brine
  5. concentrationconcentrated
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 2.5 h before it
  8. customwas quenched with water
  9. customThe mixture was purified by HPLC

Sources & evidence

ORD record
ord-8602ca6732cd401e9c94677420b037d5
Source dataset
uspto-grants-2015_09
Patent number
US09126932B2

Reaction notes

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