Methyl iodide → Ethyl 3-cyclopropyl-3-(6-(((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)(methyl)amino)pyrimidin-4-yl)propanoate

HRID 709619Notes

Reaction equation

HRID 709619 reaction equation
[CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:26]=4[F:33])=[C:21]([O:34][CH2:35][CH:36]([CH3:38])[CH3:37])[N:20]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3][CH2:2]1.[C:39](=O)([O-])[O-].[K+].[K+].IC.[H-].[Na+].[Cl-].[NH4+]>CN(C=O)C>[CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([N:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:26]=4[F:33])=[C:21]([O:34][CH2:35][CH:36]([CH3:37])[CH3:38])[N:20]=3)[CH3:39])[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 117760162Ethyl 3-cyclopropyl-3-(6-(((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)amino)pyrimidin-4-yl)propanoate

Product 1

HCID 117759747Ethyl 3-cyclopropyl-3-(6-(((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)(methyl)amino)pyrimidin-4-yl)propanoateYield 56.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of ethyl 3-cyclopropyl-3-(6-(((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)amino)pyrimidin-4-yl)propanoate (52 mg) in DMF (3.0 mL) were added potassium carbonate (21 mg) and iodomethane (20 μL), and the mixture was stirred at 40° C. for 17 hr. 60% Sodium hydride (10 mg) was added, and the mixture was stirred at room temperature for 1 hr. Saturated aqueous ammonium chloride solution was added, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (30 mg) as a colorless oil.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hr
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7566f1e99dc4439c9515f71c920c6993
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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