Trifluoroacetic acid → HCID 46927295, compound

HRID 592206Notes

Reaction equation

HRID 592206 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][C:11]([CH2:18][C:19](OC(C)(C)C)=[O:20])=[CH:10][N:9]=2)[CH:5]=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O.[NH2:33][C:34]1[N:39]=[CH:38][C:37]([N:40]2[CH2:45][CH2:44][N:43]([C:46](=[O:48])[CH3:47])[CH2:42][CH2:41]2)=[CH:36][CH:35]=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>[C:46]([N:43]1[CH2:42][CH2:41][N:40]([C:37]2[CH:36]=[CH:35][C:34]([NH:33][C:19](=[O:20])[CH2:18][C:11]3[CH:12]=[C:13]([C:14]([F:16])([F:17])[F:15])[C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=4)=[N:9][CH:10]=3)=[N:39][CH:38]=2)[CH2:45][CH2:44]1)(=[O:48])[CH3:47]

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 284116891-(4-(6-Aminopyridin-3-YL)piperazin-1-YL)ethan-1-oneHCID 68247105HCID 68247105, compound

Product 1

HCID 46927295HCID 46927295, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 2-(2′-methyl-3-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetate 189-4 (230 mg, 0.65 mmol) and TFA (1 mL) in DCM (5 mL) was stirred at room temperature for 5 hours. The solvents were evaporated to dryness under high vacuum. The crude product, 2-(2′-methyl-3-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetic acid 189-5, was dissolved in DMF (4 mL). 1-(4-(6-aminopyridin-3-yl)piperazin-1-yl)ethanone (173 mg, 0.78 mmol) and DIEA (910 uL, 5.22 mmol) were added to the solution before O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (372 mg, 0.98 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-(2′-methyl-3-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetamide 189. MS m/z 499.2 (M+1); 1H NMR 400 MHz (MeOD) δ 8.78(s, 1H), 8.48(d, 1H), 8.26(s, 1H), 7.99(s, 1H), 7.88(d, 1H), 7.42-7.36(m, 2H), 7.31(d, 1H), 3.92(s, 2H), 3.69(t, 2H), 3.65(t, 2H), 3.16(t, 2H), 3.11(t, 2H), 2.57(s, 3H), 2.09(s, 3H).

Workup

  1. customThe solvents were evaporated to dryness under high vacuum
  2. dissolutionThe crude product, 2-(2′-methyl-3-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetic acid 189-5, was dissolved in DMF (4 mL)
  3. stirringThe mixture was stirred at room temperature overnight
  4. customThe solvent was removed by rotary evaporation
  5. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-adc6f25827354a5a92620486e70326fc
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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