Diisopropylethylamine → 5-(4-Acetylpiperazin-1-yl)-N-((3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methyl)picolinamide

HRID 711255Notes

Reaction equation

HRID 711255 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[CH:11][N:10]=2)[CH:6]=[CH:5][N:4]=1.[C:19]([N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([OH:36])=O)=[N:32][CH:33]=2)[CH2:24][CH2:23]1)(=[O:21])[CH3:20].[CH3:37]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:19]([N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([NH:16][CH2:15][C:12]3[CH:13]=[C:14]([CH3:37])[C:9]([C:7]4[CH:6]=[CH:5][N:4]=[C:3]([C:2]([F:1])([F:17])[F:18])[CH:8]=4)=[N:10][CH:11]=3)=[O:36])=[N:32][CH:33]=2)[CH2:24][CH2:23]1)(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67208623(2'-(Trifluoromethyl)-2,4'-bipyridin-5-yl)methanamineHCID 672086445-(4-Acetylpiperazin-1-yl)picolinic acid

Product 1

HCID 565990285-(4-Acetylpiperazin-1-yl)-N-((3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methyl)picolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methanamine 48-1 (27 mg, 0.10 mmol), 5-(4-acetylpiperazin-1-yl)picolinic acid 48-2 (25 mg, 0.10 mmol) and HATU (38 mg, 0.10 mmol) in DMF (0.6 mL) was added DIEA (0.08 mL, 0.50 mmol). The mixture was stirred at room temperature for 2 hours. The solvent was removed by rotary evaporation. The crude product was purified by reverse phase HPLC to give 5-(4-acetylpiperazin-1-yl)-N-((3-methyl-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methyl)picolinamide 48 as a white powder. MS m/z 499.20 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 9.20 (t, 1H, J=6.4 Hz), 8.86 (d, 1H, J=5.2 Hz), 8.53 (m, 1H), 8.32 (d, 1H, J=2.8 Hz), 8.04 (s, 1H), 7.93-7.86 (m, 2H), 7.72 (m, 1H), 7.43 (dd, 1H, J1=8.8 Hz, J2=2.8 Hz), 4.52 (d, 2H, J=6.4 Hz), 3.60-3.58 (m, 4H), 3.41-3.38 (m, 4H), 2.36 (s, 3H), 2.05 (s, 3H).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-38d44a37f2ae4b84ba3866cbabb5cc43
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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