Methyl iodide → HCID 178480028, compound

HRID 2103696Notes

Reaction equation

HRID 2103696 reaction equation
[N:1]1([C@H:7]2[CH2:10][C@H:9]([C:11]3[S:12][C:13]4[CH:19]=[C:18]([C:20]5[CH:21]=[N:22][NH:23][CH:24]=5)[CH:17]=[CH:16][C:14]=4[N:15]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].I[CH3:28]>CN(C=O)C>[CH3:28][N:23]1[CH:24]=[C:20]([C:18]2[CH:17]=[CH:16][C:14]3[N:15]=[C:11]([C@H:9]4[CH2:8][C@H:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:10]4)[S:12][C:13]=3[CH:19]=2)[CH:21]=[N:22]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178419852HCID 178419852, compound

Product 1

HCID 178480028HCID 178480028, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The product of Example 51B (34.0 mg, 0.10 mmole) was dissolved in DMF (2 ml) and then cooled to 0° C. NaH (60%, 44.0 mg, 1.1 mmol) was added under N2, and the reaction was stirred at 0° C. for 0.5 hours. Iodomethane (6.8 μl, 0.11 mmole) was added, and the reaction mixture was stirred at 0° C. for 1 hour, and then slowly raised to room temperature. The mixture was quenched with saturated aqueous sodium bicarbonate and extracted with dichloromethane (4×5 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product which was purified by column chromatography (10% methanol in dichloromethane) to give 23.8 mg (67.6%) of title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.94 (d, J=8.48 1H) 7.93 (d, J=2.03 1H) 7.80 (s, 1H) 7.66, (s, 1H) 7.56 (dd, J=8.48, 2.03 1H) 3.80 (s, 3H) 3.87 (m, 1H) 3.27 (m, 1H) 2.38-2.62 (m, 4H) 1.49-1.76 (m, 6H). MS: (M+H)+=353.

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 1 hour
  2. temperatureslowly raised to room temperature
  3. customThe mixture was quenched with saturated aqueous sodium bicarbonate
  4. extractionextracted with dichloromethane (4×5 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product which
  10. customwas purified by column chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b1547276f03b42009be5f5d516d38abb
Source dataset
uspto-grants-2009_08
Patent number
US07576110B2

Reaction notes

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