HCID 23401463, compound → HCID 23401459, compound

HRID 1351729Notes

Reaction equation

HRID 1351729 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1([CH2:22][CH2:23][CH3:24])[C:11]2[NH:12][C:13]3[C:18]([C:10]=2[CH2:9][CH2:8][O:7]1)=[C:17](Br)[C:16]([F:20])=[CH:15][C:14]=3[CH3:21])[CH3:2].[C:26]([Cu])#[N:27]>CN1CCCC1=O.O>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1([CH2:22][CH2:23][CH3:24])[C:11]2[NH:12][C:13]3[C:18]([C:10]=2[CH2:9][CH2:8][O:7]1)=[C:17]([C:26]#[N:27])[C:16]([F:20])=[CH:15][C:14]=3[CH3:21])[CH3:2]

Participants

5

Reactant 2

HCID 23401463HCID 23401463, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 23401459HCID 23401459, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
220 °C

Procedure

5-Bromo-6-fluoro-8-methyl-1-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid ethyl ester (496 mg, 1.20 mmol) and CuCN (162 mg, 1.81 mmol) was dissolved in N-methyl-2-pyrrolidinone (6 mL) and the solution was divided into the 2 microwave reaction vessels (3.0 mL each). The reaction vessels were heated in microwave at 220° C. for 15 minutes. The reaction mixtures in 2 vessels were combined and then diluted with water (10 mL). The crude mixture was extracted with EtOAc (3×20 mL). The combined organic phase was washed with brine (50 mL), dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (silica, 25% EtOAc in hexanes) to give 404 mg (94%) of title compound as a white solid. 1H NMR (DMSO): 300 MHz δ 12.02 (bs, 1H), 11.33 (bs, 1H), 7.00 (d, J=9.00 Hz, 1H), 3.96 (m, 2H), 2.95 (d, J=10.3 Hz, 1H), 2.83 (t, J=3.9 Hz, 1H), 2.72 (d, J=10.3 Hz, 1H), 2.54 (s, 3H), 1.99 (m, 2H), 1.28 (m, 1H), 0.85 (m, 1H), 0.79 (t, J=5.41 Hz, 3H).

Workup

  1. customthe solution was divided into the 2 microwave reaction vessels (3.0 mL each)
  2. customThe reaction vessels
  3. extractionThe crude mixture was extracted with EtOAc (3×20 mL)
  4. washThe combined organic phase was washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (silica, 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-191df135f6fd40a3ad318e386b5d93f5
Source dataset
uspto-grants-2007_05
Patent number
US07217730B2

Reaction notes

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