Methyl iodide → HCID 59683498, compound

HRID 2389650Notes

Reaction equation

HRID 2389650 reaction equation
[Cl:1][C:2]1[C:3]2[C:47]([F:48])=[CH:46][CH:45]=[C:44]([F:49])[C:4]=2[S:5][C:6]=1[C:7]([N:9]([CH2:25][C:26]1[CH:31]=[C:30]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38](=[O:41])[NH:39][CH3:40])[CH:33]=2)[CH:29]=[CH:28][C:27]=1[O:42][CH3:43])[CH:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12][CH2:11]1)=[O:8].[H-].[Na+].I[CH3:53]>C1COCC1.O>[Cl:1][C:2]1[C:3]2[C:47]([F:48])=[CH:46][CH:45]=[C:44]([F:49])[C:4]=2[S:5][C:6]=1[C:7]([N:9]([CH2:25][C:26]1[CH:31]=[C:30]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38](=[O:41])[N:39]([CH3:53])[CH3:40])[CH:33]=2)[CH:29]=[CH:28][C:27]=1[O:42][CH3:43])[CH:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12][CH2:11]1)=[O:8]

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59683621HCID 59683621, compound

Product 1

HCID 59683498HCID 59683498, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of amide 158 (125 mg, 0.175 mmol) in THF (5 mL) is treated with sodium hydride (11 mg, 0.26 mmol, 60% dispersion in mineral oil) at 0° C. After warming to RT and stirring 0.5 h, iodomethane (0.13 mL, 0.26 mmol, 2 M solution in TBME) is added via syringe and the reaction stirred 1 h. Analysis by LC/MS at this juncture revealed the reaction is only 75% complete. Hence more sodium hydride (11 mg, 0.26 mmol, 60% dispersion in mineral oil) is added, followed after 0.5 h by iodomethane (0.13 mL, 0.26 mmol, 2 M solution in TBME). After a further hour at RT, the reaction is diluted with water (10 mL) and extracted into EtOAc (3×20 mL). The combined EtOAc phases are dried (Na2SO4) and the solvent removed in vacuo. The title compound is obtained after chromatography (gradient elution—50-80% EtOAc in heptane with 0.5% triethylamine).

Workup

  1. stirringthe reaction stirred 1 h
  2. waitAfter a further hour at RT
  3. extractionextracted into EtOAc (3×20 mL)
  4. dry with materialThe combined EtOAc phases are dried (Na2SO4)
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-1b573dc2ae6d49c8aa2d8a037571a6d9
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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