Sodium Iodide → Carbonic acid 1-(5-{(R)-(4-{amino[benzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxy)propyl ester trans-2-fluoro-cyclohexyl ester

HRID 2089656Notes

Reaction equation

HRID 2089656 reaction equation
[NH2:1][C:2](=[N:36][C:37](=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:23]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=2[F:35])[C:11]2[NH:15][C:14](=[O:16])[N:13]([C:17]3[N:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:12]=2)=[CH:5][CH:4]=1.[F:45][C@@H:46]1[CH2:51][CH2:50][CH2:49][CH2:48][C@H:47]1[O:52][C:53](=[O:59])[O:54][CH:55](Cl)[CH2:56][CH3:57].[I-].[Na+].C(=O)([O-])O.[K+]>O.CN(C=O)C>[F:45][C@@H:46]1[CH2:51][CH2:50][CH2:49][CH2:48][C@H:47]1[O:52][C:53](=[O:59])[O:54][CH:55]([O:16][C:14]1[N:13]([C:17]2[N:18]=[CH:19][CH:20]=[CH:21][N:22]=2)[N:12]=[C:11]([C@H:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:2]([NH2:1])=[N:36][C:37](=[O:44])[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)=[CH:4][CH:5]=2)[C:23]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=2[F:35])[N:15]=1)[CH2:56][CH3:57]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 516893Potassium BicarbonateHCID 86677398HCID 86677398, compoundHCID 136334027N-[1-amino-1-(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide

Product 1

HCID 54670298Carbonic acid 1-(5-{(R)-(4-{amino[benzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxy)propyl ester trans-2-fluoro-cyclohexyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of N-[1-amino-1-(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H[1,2,4]-triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 12b, 500 mg) and DMF (5 mL), carbonic acid 1-chloropropyl ester trans-2-fluorocyclohexyl ester (998 mg), sodium iodide (625 mg), and potassium hydrogen carbonate (100 mg) were added, and the resulting mixture was stirred at 40° C. for 76 hours. Water was added to the mixture, and the resulting mixture was extracted with ethyl acetate. The organic layer was sequentially washed twice with water and with saturated aqueous sodium 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 crudely purified by silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain a crudely purified product.

Workup

  1. additionwere added
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe organic layer was sequentially washed twice with water and with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe resulting mixture was filtered
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas crudely purified by silica gel column chromatography (mixed solvent of methanol-ethyl acetate)
  10. customto obtain a crudely purified product

Sources & evidence

ORD record
ord-8c8b8bc0ddf44509a5e06846969b3de6
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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