Ethylene Glycol → 2-Amino-6-(2-hydroxyethoxy)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

HRID 2080205Notes

Reaction equation

[H-].[Na+].[NH2:3][C:4]1[N:25]=[C:24](Cl)[CH:23]=[CH:22][C:5]=1[C:6]([NH:8][CH2:9][C:10]1[S:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:13][CH:14]=1)=[O:7].[CH2:27]([OH:30])[CH2:28][OH:29].[Cl-].[NH4+]>C(#N)C.O.FC(F)(F)C(O)=O.[Cu]I.ClCCl.O>[NH2:3][C:4]1[N:25]=[C:24]([O:29][CH2:28][CH2:27][OH:30])[CH:23]=[CH:22][C:5]=1[C:6]([NH:8][CH2:9][C:10]1[S:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:13][CH:14]=1)=[O:7]

Participants

Conditions

Temperature: 65 °C

Procedure

Sodium hydride (3.1 mg, 0.078 mmol, 60% in oil), catalytic amount of copper(I) iodide, 2-amino-6-chloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-102 (4.0 mg, 0.011 mmol) were added sequentially to ethyleneglycol (0.7 mL), and the solution was stirred at 65° C. for 2 hours. After further stirring at 90° C., the solution was allowed to cool to room temperature. Water, dichloromethane and an aqueous solution of saturated ammonium chloride were added to the reaction solution for extraction, which was then washed with brine, then, the solvent was evaporated in vacuo. The residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used), and trifluoroacetic acid salt of the title compound (0.26 mg, 0.00052 mmol, 4.7%) was obtained.

Workup

stirringAfter further stirring at 90° C.
temperatureto cool to room temperature
washwas then washed with brine
customthe solvent was evaporated in vacuo

Sources & evidence

ORD record: ord-23106bcd6b224a6c9f3fb4a0d85a1dc2
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932272B2

Reaction notes

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