Methyl iodide → HCID 10275159, compound

HRID 412998Notes

Reaction equation

HRID 412998 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[C:4]([CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[C:3]1[CH3:30].[H-].[Na+].[CH3:33]I>CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[C:4]([CH2:20][CH2:21][N:22]([CH3:33])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[C:3]1[CH3:30]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10274190HCID 10274190, compound

Product 1

HCID 10275159HCID 10275159, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of tert-butyl 2-[1,2-dimethyl-5-(phenylsulfonyl)-1H-indol-3-yl]ethylcarbamate (2.99 g, 6.98 mmol) in DMF (20.0 mL) was added to a 0° C. suspension of 60% sodium hydride (0.75 g, 18.82 mmol) in DMF (5.0 mL) and stirred at room temperature for one hour. Methyl iodide (0.55 mL, 8.83 mmol) was added and the reaction was stirred at room temperature for 22 hours. The reaction was cooled to 0° C., quenched with water (10.0 mL) and filtered. The filtrate was concentrated in vacuo, combined with the previously filtered solid and partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo and recrystallized from EtOAc/hexane to give 2.56 g (83%) of colorless crystals as the title compound: mp 147.1-149.0° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.15-8.10 (m, 1H), 7.92 (d, J=7.1 Hz, 2H), 7.62-7.53 (m, 5H), 3.67 (s, 3H), 3.32 (m, 2H), 2.91-2.88 (m, 2H), 2.79 (br, 3H), 2.33 (br, 3H), 1.35-0.99 (2 br, 9H); 13C NMR (100 MHz, DMSO-d6) δ 154.4, 142.9, 138.0, 137.1, 132.7, 130.4, 129.3, 126.9, 126.7, 119.0, 117.7, 109.9, 109.4, 77.7, 48.8, 33.7, 29.7, 27.9, 27.4, 22.0, 9.8; IR (diffuse reflectance) 1692, 1482, 1446, 1364, 1303, 1219, 1192, 1164, 1152, 1140, 1095, 725, 689, 655, 609 cm−1; HRMS (FAB) calcd for C24H30N2O4S+H 443.2004, found 443.2025. Anal. Calcd for C24H30N2O4S: C, 65.13; H. 6.83; N, 6.33. Found: C, 65.06; H, 6.86; N, 6.33.

Workup

  1. stirringthe reaction was stirred at room temperature for 22 hours
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with water (10.0 mL)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompartitioned between ethyl acetate and water
  7. customThe layers were separated
  8. washthe organic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customrecrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-8f63df259c474d4089f3992eb298aaf0
Source dataset
uspto-grants-2003_05
Patent number
US06565829B2

Reaction notes

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