Triethylamine → N-[3,5-bis(trifluoromethyl)phenyl]-4-(2-{[(3-chloro-2,5,6-trifluoropyridin-4-yl)amino]methyl}phenyl)piperazine-1-carboxamide

HRID 907571Notes

Reaction equation

HRID 907571 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[CH2:28][NH2:29])[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.[Cl:39][C:40]1[C:41]([F:49])=[N:42][C:43]([F:48])=[C:44]([F:47])[C:45]=1F>C(#N)C.CO>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([NH:13][C:14]([N:16]2[CH2:17][CH2:18][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[CH2:28][NH:29][C:45]3[C:44]([F:47])=[C:43]([F:48])[N:42]=[C:41]([F:49])[C:40]=3[Cl:39])[CH2:20][CH2:21]2)=[O:15])[CH:4]=[C:3]([C:2]([F:1])([F:30])[F:31])[CH:8]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1371833-Chloro-2,4,5,6-tetrafluoropyridineHCID 590139384-(2-Aminomethyl-phenyl)piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)amide

Product 1

HCID 59013847N-[3,5-bis(trifluoromethyl)phenyl]-4-(2-{[(3-chloro-2,5,6-trifluoropyridin-4-yl)amino]methyl}phenyl)piperazine-1-carboxamideYield 22.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

4-(2-Aminomethyl-phenyl)piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)amide (50 mg, 0.11 mmol, prepared in Example 26b) was dissolved in 500 μL of acetonitrile. Then, triethylamine (20 μL, 0.14 mmol) was added, followed by 3-chloro-2,4,5,6-tetrafluoropyridine (17 μL, 0.15 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted to 2 mL in volume with methanol and the mixture was purified by reverse phase HPLC to give 15 mg of the product as a white solid. 1H NMR (CDCl3) δ 7.88 (s, 2H), 7.52 (s, 1H), 7.31-7.38 (m, 2H), 7.15-7.22 (m, 2H), 6.70 (s, 1H), 5.88 (br t, 1H), 4.85 (dd, 2H), 3.71 (m, 4H), 3.02 (t, 4H) ppm.

Workup

  1. customthe mixture was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d3a5d000c5ef455cb043e016117159cc
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

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