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

HRID 1036282Notes

Reaction equation

HRID 1036282 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:16][C:17]([O:19]C(C)(C)C)=O)[CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=1)#[N:2].[C:24](O)([C:26](F)(F)F)=[O:25].N1C=CN=CC=1[C:37]1[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:64]2[N:65]=[CH:66][CH:67]=C[C:63]=2[N:62]=N1>C(Cl)Cl>[C:24]([N:62]1[CH2:63][CH2:64][N:65]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:17](=[O:19])[CH2:16][C:5]3[CH:6]=[CH:7][C:8]([C:9]4[CH:14]=[CH:13][N:12]=[C:11]([F:15])[CH:10]=4)=[C:3]([C:1]#[N:2])[CH:4]=3)=[N:41][CH:42]=2)[CH2:66][CH2:67]1)(=[O:25])[CH3:26]

Participants

7

Reactant 5

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 592592255-(Pyrazin-2-yl)pyridin-2-amineHCID 68247402Tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate

Product 1

HCID 58447806N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetate 206-5 (35 mg, 0.11 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-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetic acid 206-6, was dissolved in DMF (2 mL). 5-(pyrazin-2-yl)pyridin-2-amine (23 mg, 0.13 mmol) and DIEA (98 uL, 0.56 mmol) were added to the solution before O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (64 mg, 0.17 mmol). The mixture was stirred at room temperature overnight. 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-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetamide 206. MS m/z 411.2 (M+1); 1H NMR 400 MHz (MeOD) δ 9.09 (s, 1H), 9.01 (s, 1H), 8.66 (dd, 1H), 8.52 (d, 1H), 8.42 (dd, 1H), 8.32 (d, 1H), 8.25 (d, 1H), 7.92 (d, 1H), 7.81 (dd, 1H), 7.64 (d, 1H), 7.52 (dt, 1H), 7.28 (s, 1H), 3.93 (s, 2H).

Workup

  1. customThe solvents were evaporated to dryness under high vacuum
  2. dissolutionThe crude product, 2-(3-cyano-4-(2-fluoropyridin-4-yl)phenyl)acetic acid 206-6, was dissolved in DMF (2 mL)
  3. stirringThe mixture was stirred at room temperature overnight
  4. stirringThe mixture was stirred at room temperature overnight
  5. customThe solvent was removed by rotary evaporation
  6. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-31dbcf255b05441e83e697cb02331c6c
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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