Ethanolamine → 2-Amino-6-(4-chloro-benzylamino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

HRID 2080196Notes

Reaction equation

HRID 2080196 reaction equation
[NH2:1][C:2]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5].C1C=CC(CC(NCN[C@H](C(O)=O)CC2C=CC([N+]([O-])=O)=CC=2)=O)=CC=1.[Cl:51][C:52]1[CH:59]=[CH:58][C:55]([CH2:56][NH2:57])=[CH:54][CH:53]=1.C(N(CC)C(C)C)(C)C.C(CN)O.FC(F)(F)C(O)=O>CS(C)=O.O>[NH2:1][C:2]1[N:23]=[C:22]([NH:57][CH2:56][C:55]2[CH:58]=[CH:59][C:52]([Cl:51])=[CH:53][CH:54]=2)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5]

Participants

9

Reactant 6

HCID 700EthanolamineHCID 6422Trifluoroacetic acidHCID 660364-ChlorobenzylamineHCID 81531Diisopropylethylamine2×HCID 188218A-101HCID 231304982-aminochloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide

Product 1

HCID 231308102-Amino-6-(4-chloro-benzylamino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamideYield 24%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-amino-6-chloro-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide described in Example A-101 (35 mg, 0.10 mmol) in dimethylsulfoxide (1mL) were added 4-chlorobenzylamine (234 μl, 1.92 mmol) and N,N-diisopropylethylamine (1.0 mL, 5.74 mmol), and the solution was stirred at 140° C. for 2.5 days. Ethanolamine (116 μl, 1.92 mmol) and N,N-diisopropylethylamine (1.0 mL, 5.74 mmol) were added to the reaction mixture, which was then further stirred at 140° C. for 2.5 days. Water was added to the reaction mixture, which was then extracted with ethyl acetate, the organic layer was sequentially washed with water and brine, dried over anhydrous sodium sulfate, and then, concentrated in vacuo. The obtained residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used), and the title compound (13.8 mg, 0.024 mmol, 24%) was obtained as a trifluoroacetic acid salt.

Workup

  1. stirringwas then further stirred at 140° C. for 2.5 days
  2. extractionwas then extracted with ethyl acetate
  3. washthe organic layer was sequentially washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe obtained residue was purified by reverse phase high performance liquid chromatography (acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid) was used)

Sources & evidence

ORD record
ord-d88497f801ef4f488061673c3d0b26d8
Source dataset
uspto-grants-2011_04
Patent number
US07932272B2

Reaction notes

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