Sodium Iodide → HCID 76166086, compound

HRID 2089644Notes

Reaction equation

HRID 2089644 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.[I-].[Na+].C(=O)([O-])O.[K+].[CH:54]1([O:60][C:61](=[O:68])[C:62]([CH3:67])([CH3:66])[C:63]([OH:65])=[O:64])[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]1>O.C(OCC)(=O)C.CN(C=O)C>[CH:54]1([O:60][C:61](=[O:68])[C:62]([CH3:66])([CH3:67])[C:63]([O:65][CH2:35][O:34][C:32]2[N:31]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:30]=[C:29]([CH:15]([NH:14][C:11]3[CH:12]=[CH:13][C:8]([C:7]([NH2:43])=[N:6][C:5]([O:4][CH2:3][C:2]([CH3:46])([CH3:45])[CH3:1])=[O:44])=[CH:9][CH:10]=3)[C:16]3[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH2:25][CH2:26][OH:27])[C:17]=3[F:28])[N:33]=2)=[O:64])[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 516893Potassium BicarbonateHCID 674699622,2-Dimethylmalonic acid monocyclohexyl esterHCID 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 76166086HCID 76166086, compoundYield 96.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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, 80 mg) and DMF (5 mL), sodium iodide (183 mg), potassium hydrogen carbonate (85.5 mg), and 2,2-dimethylmalonic acid monocyclohexyl ester (261 mg) were added, and the resulting mixture was stirred at room temperature for 3 days. Ethyl acetate (30 mL) and water (10 mL) were added to the mixture, and the resulting mixture was shaken, after which the organic layer was collected. Ethyl acetate (20 mL) was added to the aqueous layer, and the resulting mixture was shaken, after which the organic layer was collected. All the organic layers were combined, washed with saturated aqueous sodium chloride solution (10 mL), 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 heptane-ethyl acetate) to obtain the captioned compound (97.9 mg).

Workup

  1. additionwere added
  2. stirringthe resulting mixture was shaken
  3. customafter which the organic layer was collected
  4. additionEthyl acetate (20 mL) was added to the aqueous layer
  5. stirringthe resulting mixture was shaken
  6. customafter which the organic layer was collected
  7. washwashed with saturated aqueous sodium chloride solution (10 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe resulting mixture was filtered
  10. customthe filtrate obtained
  11. concentrationwas concentrated under reduced pressure
  12. customThe residue obtained
  13. customwas purified by NAM silica gel column chromatography (mixed solvent of heptane-ethyl acetate)

Sources & evidence

ORD record
ord-aa4fad03ea044ab1b6e1dcfafee72f45
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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