Trifluoroacetic acid → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetamide

HRID 592240Notes

Reaction equation

HRID 592240 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:15][C:16]([O:18]C(C)(C)C)=O)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=1.C(O)(C(F)(F)F)=O.FC1C=C(CC(O)=O)C=CC=1C1C=CN=C(F)C=1.[NH2:48][C:49]1[N:54]=[CH:53][C:52]([N:55]2[CH2:60][CH2:59][N:58]([C:61](=[O:63])[CH3:62])[CH2:57][CH2:56]2)=[CH:51][CH:50]=1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C>[C:61]([N:58]1[CH2:57][CH2:56][N:55]([C:52]2[CH:51]=[CH:50][C:49]([NH:48][C:16](=[O:18])[CH2:15][C:4]3[CH:5]=[CH:6][C:7]([C:8]4[CH:13]=[CH:12][N:11]=[C:10]([F:14])[CH:9]=4)=[C:2]([F:1])[CH:3]=3)=[N:54][CH:53]=2)[CH2:60][CH2:59]1)(=[O:63])[CH3:62]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 284116891-(4-(6-Aminopyridin-3-YL)piperazin-1-YL)ethan-1-oneHCID 584476772-(3-Fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetic acidHCID 58447777Tert-butyl 2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetate

Product 1

HCID 58447812N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetate 207-5 (100 mg, 0.33 mmol) and TFA (0.5 mL) in DCM (3 mL) was stirred at room temperature for 5 hours. The solvents were evaporated to dryness under high vacuum. The crude product, 2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetic acid 207-6 (50 mg, 0.20 mmol), was dissolved in DMF (2 mL), 1-(4-(6-aminopyridin-3-yl)piperazin-1-yl)ethanone (53 mg, 0.24 mmol) and DIEA (174 uL, 1.0 mmol) were added to the solution before O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (114 mg, 0.30 mmol). The mixture was stirred at room temperature overnight. The solvent was removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-fluoropyridin-4-yl)phenyl)acetamide 207. MS m/z 452.2 (M+1); 1H NMR 400 MHz (MeOD) δ 8.21 (d, 1H), 7.96 (d, 1H), 7.88 (d, 1H), 7.57-7.51 (m, 1H), 7.48-7.45 (m, 1H), 7.37 (dd, 1H), 7.30-7.21 (m, 3H), 3.75 (s, 2H), 3.68 (t, 2H), 3.63 (t, 2H), 3.14 (t, 2H), 3.09 (t, 2H, J=5.2 Hz), 2.09 (s, 3H).

Workup

  1. customThe solvents were evaporated to dryness under high vacuum
  2. stirringThe mixture was stirred at room temperature overnight
  3. customThe solvent was removed by rotary evaporation
  4. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b5e428389d1348e0866da00bc48ab4b4
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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