Methyl iodide → N-((5-ethoxy-2-fluoro-3-isopropoxyphenyl)(4-(1-methyl-1H-pyrazol-4-yl)-1-trityl-1H-imidazol-2-yl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamine

HRID 2105036Notes

Reaction equation

HRID 2105036 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[N:7]=[C:8]([CH:30]([C:44]3[CH:49]=[C:48]([O:50][CH2:51][CH3:52])[CH:47]=[C:46]([O:53][CH:54]([CH3:56])[CH3:55])[C:45]=3[F:57])[NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]4[N:42]=[C:41]([CH3:43])[O:40][N:39]=4)=[CH:34][CH:33]=3)[N:9]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:10]=2)[CH:3]=[N:2]1.[H-].[Na+].[CH3:60]I>C1COCC1>[CH2:51]([O:50][C:48]1[CH:47]=[C:46]([O:53][CH:54]([CH3:56])[CH3:55])[C:45]([F:57])=[C:44]([CH:30]([C:8]2[N:9]([C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:10]=[C:6]([C:4]3[CH:5]=[N:1][N:2]([CH3:60])[CH:3]=3)[N:7]=2)[NH:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]3[N:42]=[C:41]([CH3:43])[O:40][N:39]=3)=[CH:34][CH:33]=2)[CH:49]=1)[CH3:52]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68815685N-((4-(1H-pyrazol-4-yl)-1-trityl-1H-imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamine

Product 1

HCID 68814350N-((5-ethoxy-2-fluoro-3-isopropoxyphenyl)(4-(1-methyl-1H-pyrazol-4-yl)-1-trityl-1H-imidazol-2-yl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamineYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Intermediate 237.1 (30 mg, 0.04 mmol) in THF (1 mL) at 0° C. was added NaH (3.16 mg, 0.08 mmol), stirred at 0° C. for 30 min, then MeI was added and the reaction mixture was warmed up to rt over 1 h. The reaction mixture was then partitioned between EtOAc and sat. NH4Cl, the organic layer was dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes, gradient) to afford 20 mg (62%) of Intermediate 237.2.

Workup

  1. temperaturethe reaction mixture was warmed up to rt over 1 h
  2. customThe reaction mixture was then partitioned between EtOAc and sat. NH4Cl
  3. dry with materialthe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes, gradient)

Sources & evidence

ORD record
ord-240d32b940be48dfb4ec44ed50fa5ade
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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