Potassium Bicarbonate → Carbonic acid 1-(5-{(4-{amino[4-methylbenzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxy)ethyl ester (1R,2R)-2-methylcyclohexyl ester

HRID 2089647Notes

Reaction equation

HRID 2089647 reaction equation
[NH2:1][C:2](=[N:36][C:37](=[O:45])[C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH: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+].[CH3:51][C@@H:52]1[CH2:57][CH2:56][CH2:55][CH2:54][C@H:53]1[O:58][C:59](=[O:64])[O:60][CH:61](Cl)[CH3:62]>CN(C=O)C>[CH3:51][C@@H:52]1[CH2:57][CH2:56][CH2:55][CH2:54][C@H:53]1[O:58][C:59](=[O:64])[O:60][CH:61]([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]([CH:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([NH2:1])=[N:36][C:37](=[O:45])[C:38]3[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=3)=[CH:8][CH:7]=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)[CH3:62]

Participants

5

Reactant 3

HCID 516893Potassium BicarbonateHCID 68212867Carbonic acid 1-chloroethyl ester (1R,2R)-2-methylcyclohexyl esterHCID 136334026N-[1-amino-1-(4-{[[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]-4-methylbenzamide

Product 1

HCID 86677393Carbonic acid 1-(5-{(4-{amino[4-methylbenzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxy)ethyl ester (1R,2R)-2-methylcyclohexyl esterYield 43.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of N-[1-amino-1-(4-{[[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]-4-methylbenzamide (230 mg) and DMF (3 mL), potassium hydrogen carbonate (113 mg) and carbonic acid 1-chloroethyl ester (1R,2R)-2-methylcyclohexyl ester (250 mg) were sequentially added, and the resulting mixture was stirred at 55° C. for 24 hours and at room temperature for another 2 days. The reaction solution was purified by reverse phase silica gel column chromatography (mixed solvent of acetonitrile-water) to obtain the captioned compound (129.2 mg).

Workup

  1. additionwere sequentially added
  2. customThe reaction solution was purified by reverse phase silica gel column chromatography (mixed solvent of acetonitrile-water)

Sources & evidence

ORD record
ord-e5fc7b291fdf41cd93af9e5e1bf5a844
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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