Cesium carbonate → Ethyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-8-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

HRID 515733Notes

Reaction equation

HRID 515733 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:6]3=[CH:5][C:4]=2[C:3]=1[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:37][CH:38]([CH3:40])[CH3:39])=[C:33]([CH:36]=1)[C:34]#[N:35]>CN(C=O)C>[C:34]([C:33]1[CH:36]=[C:29]([CH:30]=[CH:31][C:32]=1[O:37][CH:38]([CH3:40])[CH3:39])[CH2:28][O:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:6]3=[CH:5][C:4]=2[C:3]=1[CH3:20])#[N:35]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 668477035-(Chloromethyl)-2-(propan-2-yloxy)benzonitrileHCID 67249573ethyl 2-(7-hydroxy-8-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 67248141Ethyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-8-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of ethyl 2-(7-hydroxy-8-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (100 mg, 0.366 mmol) in DMF (3 mL) was added cesium carbonate (155 mg, 0.476 mmol), followed by 5-(chloromethyl)-2-isopropoxybenzonitrile (100 mg, 0.476 mmol). The reaction mixture was heated at 65° C. for 15 h and cooled down. The solid was filtered and washed with ethyl acetate. The combined solvent was evaporated, and the residue was purified by column chromatography to give the title compound (130 mg) as a colorless oil. LCMS m/z=447.7 [M+H]+; 1H NMR (400 ME-1z, CDCl3) δ ppm 1.32 (t, J=7.1 Hz, 3H), 1.42 (d, J=6.0 Hz, 6H), 2.25-2.32 (m, 1H), 2.42 (s, 3H), 2.58 (dd, J=16.0, 8.4 Hz, 1H), 2.82-2.92 (m, 2H), 3.73-3.80 (m, 1H), 3.95-4.02 (m, 1H), 4.08-4.15 (m, 1H), 4.20-4.27 (m, 2H), 4.62-4.69 (m, 1H), 4.96 (s, 2H), 6.13 (s, 1H), 6.83 (d, J=8.7 Hz, 1H), 6.97 (d, J=8.7 Hz, 1H), 7.01 (d, J=8.7 Hz, 1H), 7.59 (dd, J=8.6, 2.2 Hz, 1H), 7.63 (d, J=2.1 Hz, 1H).

Workup

  1. temperaturecooled down
  2. filtrationThe solid was filtered
  3. washwashed with ethyl acetate
  4. customThe combined solvent was evaporated
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ada90ee5872f43f897b07b23a5b4fd8a
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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