Methyl iodide → HCID 22462753, compound

HRID 1937187Notes

Reaction equation

HRID 1937187 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[OH:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[C:19]([CH3:29])[CH:18]=3)=[C:14]([C:30]3[CH:35]=[CH:34][C:33]([NH:36][C:37]([CH:39]4[CH2:43][CH2:42][C:41](=[O:44])[N:40]4[CH3:45])=[O:38])=[CH:32][CH:31]=3)[S:13][C:12]=2[CH:46]=1.[H-].[Na+].CI.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[OH:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[C:19]([CH3:29])[CH:18]=3)=[C:14]([C:30]3[CH:35]=[CH:34][C:33]([N:36]([CH3:1])[C:37]([CH:39]4[CH2:43][CH2:42][C:41](=[O:44])[N:40]4[CH3:45])=[O:38])=[CH:32][CH:31]=3)[S:13][C:12]=2[CH:46]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 22462748HCID 22462748, compound

Product 1

HCID 22462753HCID 22462753, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of 6-hydroxy-3-[3-methyl-4-(1-pyrrolidinylmethyl)benzyl]-2-[4-(1-methyl-5-oxopyrrolidin-2-ylcarbonylamino)phenyl]benzo[b]thiophene from Example 29, Part B (150 mg; 0.264 mmol) in 5 mL of dry DMF was treated with NaH (16 mg; 0.37 mmol). After 1 hr, methyl iodide (0.017 mL; 0.264 mmol) was quickly added via a syringe. The resulting mixture was stirred at 0° C. for 30 min, then it was allowed to warm to ambient temperature. The reaction mixture was poured into saturated aqueous NH4Cl and EtOAc (25 mL each). The aqueous layer was extracted with 5% MeOH/EtOAc (2×25 mL). The combined organics were dried over K2CO3, filtered and concentrated in vacuo. The crude residue was purified by radial chromatography (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH) afforded 37 mg (24%) of the title product as a yellow oil.

Workup

  1. temperatureto warm to ambient temperature
  2. extractionThe aqueous layer was extracted with 5% MeOH/EtOAc (2×25 mL)
  3. dry with materialThe combined organics were dried over K2CO3
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by radial chromatography (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH)

Sources & evidence

ORD record
ord-ec0ad8fcf5994818967cd56d92d54bd6
Source dataset
uspto-grants-2002_05
Patent number
US06391901B1

Reaction notes

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