Methyl iodide → HCID 86597672, compound

HRID 547764Notes

Reaction equation

HRID 547764 reaction equation
[C:1]([NH:4][C@@H:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[CH:14][C:13]([N:16]([CH3:36])[C:17](=[O:35])[C:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=3)([CH3:20])[CH3:19])=[C:12]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=3[CH3:44])[CH:11]=2)[CH2:6]1)(=[O:3])[CH3:2].[CH3:45][Si]([N-][Si](C)(C)C)(C)C.[K+].IC.C(OCC)(=O)C>O1CCCC1>[C:1]([N:4]([CH3:45])[C@@H:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[CH:14][C:13]([N:16]([CH3:36])[C:17](=[O:35])[C:18]([C:21]3[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[C:23]([C:31]([F:32])([F:33])[F:34])[CH:22]=3)([CH3:20])[CH3:19])=[C:12]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=3[CH3:44])[CH:11]=2)[CH2:6]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86597673HCID 86597673, compound

Product 1

HCID 86597672HCID 86597672, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 146 mg (0.234 mmol) (R)—N-[6-(3-acetylamino-pyrrolidin-1-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide in 5 ml tetrahydrofuran were added dropwise at room temperature 0.31 ml (0.28 mmol) of a 0.91 N potassium bis(trimethylsilyl)amide solution in tetrahydrofuran. After stirring at room temperature for 30 min. 43 mg (30 mmol) iodomethane were added. The reaction mixture was stirred at room temperature for 18 h, followed by dilution with 10 ml ethyl acetate and washing with 10 ml saturated sodium carbonate solution. The combined organic layers were dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography to give 130 mg (87%) of the title compound as a white foam.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 h
  2. washwashing with 10 ml saturated sodium carbonate solution
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c03bb29c721f4440a0374ba3a60dc3aa
Source dataset
uspto-grants-2011_05
Patent number
US07939533B2

Reaction notes

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