Tetrahydrofuran → tert-Butyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

HRID 515722Notes

Reaction equation

HRID 515722 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:12]3=[C:11](I)[C:10]=2[CH:9]=1)#[N:2].[CH2:36]1COCC1.[Cl-].C[Zn+]>>[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:12]3=[C:11]([CH3:36])[C:10]=2[CH:9]=1)#[N:2]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 86654873tert-Butyl 2-(7-(3-cyano-4-isopropoxybenzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateHCID 178477797HCID 178477797, compound

Product 1

HCID 67249930tert-Butyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 81%

Conditions

Temperature
70 °C

Procedure

tert-Butyl 2-(7-(3-cyano-4-isopropoxybenzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.717 g, 1.223 mmol) was dissolved in anhydrous THF (12.2 mL, 1.223 mmol). The solution was degassed with nitrogen for about 5 min using a syringe needle. Bis(tri-t-butylphosphine)Pd(0) (0.056 g, 0.110 mmol) and 2.0 M methylzinc chloride in THF (1.83 mL, 3.67 mmol) were added. The reaction vessel was purged with nitrogen, sealed, and heated at 70° C. After 2 h, the reaction mixture was cooled to 25° C. and slowly added saturated NaHCO3 (5 mL). After stirring for about 5 min, the reaction was diluted with EtOAc (20 mL), filtered through a celite pad, and the celite pad was washed with EtOAc (3×20 mL). The organic layer was washed with water (2×20 mL), brine (10 mL), and dried over MgSO4. The solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography to give the title compound as an oil (0.470 g). LCMS m/z=475.4 [M+H]+; 1H NMR (400 MHz, Acetonitrile-d3) δ ppm 1.36 (d, J=5.94 Hz, 6H), 1.41 (s, 9H), 2.19 (s, 3H), 2.27-2.37 (m, 1H), 2.46 (dd, J=15.66, 9.22 Hz, 1H), 2.72-2.86 (m, 2H), 3.60-3.69 (m, 1H), 3.93 (m, 1H), 4.00-4.10 (m, 1H), 4.75 (dt, J=12.13, 6.06 Hz, 1H), 5.03 (s, 2H), 6.77 (dd, J=8.72, 2.40 Hz, 1H), 7.00 (d, J=2.40 Hz, 1H), 7.11 (d, J=8.72 Hz, 1H), 7.13 (d, J=8.72 Hz, 1H), 7.63-7.68 (m, 1H), 7.69 (d, J=2.27 Hz, 1H).

Workup

  1. customThe solution was degassed with nitrogen for about 5 min
  2. customThe reaction vessel was purged with nitrogen
  3. customsealed
  4. temperaturethe reaction mixture was cooled to 25° C.
  5. additionthe reaction was diluted with EtOAc (20 mL)
  6. filtrationfiltered through a celite pad
  7. washthe celite pad was washed with EtOAc (3×20 mL)
  8. washThe organic layer was washed with water (2×20 mL), brine (10 mL)
  9. dry with materialdried over MgSO4
  10. customThe solvent was evaporated in vacuo
  11. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-114997860a9045ecb5e8859e531c2f40
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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