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)ethyl ester (1S,2S)-2-fluorocyclohexyl ester

HRID 2089653Notes

Reaction equation

HRID 2089653 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.C(=O)([O-])O.[K+].[F:50][C@H:51]1[CH2:56][CH2:55][CH2:54][CH2:53][C@@H:52]1[O:57][C:58](=[O:63])[O:59][CH:60](Cl)[CH3:61].[I-].[Na+]>CN(C=O)C>[F:50][C@H:51]1[CH2:56][CH2:55][CH2:54][CH2:53][C@@H:52]1[O:57][C:58](=[O:63])[O:59][CH:60]([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)[CH3:61]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 516893Potassium BicarbonateHCID 68212831Carbonic acid 1-chloroethyl ester (1S,2S)-2-fluorocyclohexyl esterHCID 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 54670201Carbonic 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)ethyl ester (1S,2S)-2-fluorocyclohexyl esterYield 41.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °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 (200 mg) and DMF (3 mL), potassium hydrogen carbonate (200 mg), carbonic acid 1-chloroethyl ester (1S,2S)-2-fluorocyclohexyl ester (200 mg), and sodium iodide (100 mg) were sequentially added, and the resulting mixture was stirred at 55° C. for 24 hours. The reaction mixture was crudely purified by NAM silica gel column chromatography (mixed solvent of ethyl acetate-methanol) to obtain the captioned compound (110 mg) as a crudely purified product.

Workup

  1. additionwere sequentially added
  2. customThe reaction mixture was crudely purified by NAM silica gel column chromatography (mixed solvent of ethyl acetate-methanol)

Sources & evidence

ORD record
ord-caca872cbff94165a013276f47622d5f
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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