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

HRID 711277Notes

Reaction equation

HRID 711277 reaction equation
[F:1][C:2]1[C:3]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[N:4][CH:5]=[C:6]([CH2:8][NH2:9])[CH:7]=1.[C:20]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[CH:31][C:32]([C:35](O)=[O:36])=[N:33][CH:34]=2)[CH2:25][CH2:24]1)(=[O:22])[CH3:21].CN(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:20]([N:23]1[CH2:24][CH2:25][N:26]([C:29]2[CH:30]=[CH:31][C:32]([C:35]([NH:9][CH2:8][C:6]3[CH:7]=[C:2]([F:1])[C:3]([C:10]4[CH:15]=[CH:14][N:13]=[C:12]([C:16]([F:19])([F:17])[F:18])[CH:11]=4)=[N:4][CH:5]=3)=[O:36])=[N:33][CH:34]=2)[CH2:27][CH2:28]1)(=[O:22])[CH3:21]

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 672086445-(4-Acetylpiperazin-1-yl)picolinic acidHCID 67208645(3-Fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methanamine

Product 1

HCID 565975175-(4-Acetylpiperazin-1-yl)-N-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methyl)picolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methanamine 84-2 (54 mg, 0.20 mmol), 5-(4-acetylpiperazin-1-yl)picolinic acid 48-2 (50 mg, 0.20 mmol) and HATU (76 mg, 0.20 mmol) in DMF (0.9 mL) was added DIEA (0.16 mL, 1.00 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-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methyl)picolinamide 84 as a white powder. MS m/z 503.20 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 9.28 (t, 1H, J=6.4 Hz), 8.92 (d, 1H, J=5.2 Hz), 8.62 (m, 1H), 8.32 (m, 2H), 8.20 (d, 1H, J=4.8 Hz), 7.88-7.82 (m, 2H), 7.43 (dd, 1H, J1=9.0 Hz, J2=3.2 Hz), 4.59 (d, 2H, J=6.4 Hz), 3.61-3.58 (m, 4H), 3.41-3.39 (m, 4H), 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-451e8d6e2d6e4e4f84e04e3efa62e27e
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

Loading…