Methyl iodide → HCID 60083716, compound

HRID 1883139Notes

Reaction equation

HRID 1883139 reaction equation
[C:1]([C@@H:3]([NH:12][C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[NH:21][C:22]([C:24]1[N:25]([CH3:33])[C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)#[N:2].[H-].[Na+].[CH3:36]I>CN(C=O)C>[C:1]([C@@H:3]([NH:12][C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[NH:21][C:22]([C:24]1[N:25]([CH3:33])[C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:36])=[CH:7][CH:6]=1)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 60083676HCID 60083676, compound2×

Product 1

HCID 60083716HCID 60083716, compoundYield 70.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-Methyl-1H-indole-2-carboxylic acid {(1S,2R)-2-[(S)-1-cyano-2-(4-hydroxy-phenyl)-ethylcarbamoyl]cyclohexyl}-amide (compound 34, 102 mg, 0.229 mmol) in 3 mL of anhydrous DMF, was added sodium hydride powder (15 mg, 0.594 mmol). The reaction mixture was stirred for 5 min. while gas evolution subsided, then methyl iodide (0.2 mL, 3.1 mmol) was added. The reaction mixture was partitioned between 50 mL of water and 50 mL of ethyl acetate, the separated organic layer was washed with water (2×50 mL), dried with sodium sulfate, filtered, concentrated and purified by column chromatography (50:50, ethyl acetate/hexanes) to give 74 mg (70%) of 1-methyl-1H-indole-2-carboxylic acid ((1S,2R)-2-{[(S)-cyano-(4-methoxy-benzyl)-methyl]-carbamoyl}-cyclohexyl)-amide as a white amorphous solid. MS: 459 (M+H+).

Workup

  1. customThe reaction mixture was partitioned between 50 mL of water and 50 mL of ethyl acetate
  2. washthe separated organic layer was washed with water (2×50 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography (50:50, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-065a14815597464ca783be5ebeacf3e2
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

Loading…