Sodium Iodide → HCID 68212832, compound

HRID 2089640Notes

Reaction equation

HRID 2089640 reaction equation
[CH3:1][C:2]([CH3:46])([CH3:45])[CH2:3][O:4][C:5](=[O:44])[N:6]=[C:7]([NH2:43])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH:15]([C:29]2[N:33]=[C:32]([O:34][CH2:35]Cl)[N:31]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:30]=2)[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH2:25][CH2:26][OH:27])[C:17]=2[F:28])=[CH:10][CH:9]=1.C(=O)([O-])O.[K+].[I-].[Na+].[CH:54]1([C:60]([OH:62])=[O:61])[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]1.[Cl-].[NH4+]>CN(C=O)C>[NH2:43][C:7](=[N:6][C:5]([O:4][CH2:3][C:2]([CH3:46])([CH3:45])[CH3:1])=[O:44])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH:15]([C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH2:25][CH2:26][OH:27])[C:17]=2[F:28])[C:29]2[N:33]=[C:32]([O:34][CH2:35][O:62][C:60]([CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)=[O:61])[N:31]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:30]=2)=[CH:10][CH:9]=1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 7413Cyclohexanecarboxylic acidHCID 25517Ammonium ChlorideHCID 516893Potassium BicarbonateHCID 67470504[1-amino-1-[4-({(5-chloromethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}amino)phenyl]methylidene]carbamic acid 2,2-dimethylpropyl ester

Product 1

HCID 68212832HCID 68212832, compoundYield 89.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of [1-amino-1-[4-({(5-chloromethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}amino)phenyl]methylidene]carbamic acid 2,2-dimethylpropyl ester (Example 2b, 120 mg), potassium hydrogen carbonate (131 mg), and DMF (16 mL), sodium iodide (140 mg) and cyclohexanecarboxylic acid (163 mg) were added, and the resulting mixture was stirred at 45° C. overnight. After cooling the reaction mixture to room temperature, ice and saturated aqueous ammonium chloride solution were added thereto, and the resulting mixture was extracted three times with a mixture of THF and ethyl acetate. The organic layer was collected, washed with saturated aqueous ammonium chloride solution, and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (123 mg).

Workup

  1. additionwere added
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. extractionthe resulting mixture was extracted three times
  4. additionwith a mixture of THF and ethyl acetate
  5. customThe organic layer was collected
  6. washwashed with saturated aqueous ammonium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe resulting mixture was filtered
  9. customthe filtrate obtained
  10. concentrationwas concentrated under reduced pressure
  11. customThe residue obtained
  12. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

Sources & evidence

ORD record
ord-2cb65d0adad14198a63a76085802c814
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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