Acetyl chloride → 6-(4-acetylpiperazin-1-yl)-N-((3-fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methyl)nicotinamide

HRID 711253Notes

Reaction equation

HRID 711253 reaction equation
[F:1][C:2]1[C:3]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[N:4][CH:5]=[C:6]([CH2:8][NH:9][C:10](=[O:23])[C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[N:13][CH:12]=2)[CH:7]=1.CCN(C(C)C)C(C)C.[C:43](Cl)(=[O:45])[CH3:44]>C(Cl)Cl.C(OCC)(=O)C>[C:43]([N:20]1[CH2:21][CH2:22][N:17]([C:14]2[CH:15]=[CH:16][C:11]([C:10]([NH:9][CH2:8][C:6]3[CH:7]=[C:2]([F:1])[C:3]([C:24]4[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:31])[F:32])[CH:25]=4)=[N:4][CH:5]=3)=[O:23])=[CH:12][N:13]=2)[CH2:18][CH2:19]1)(=[O:45])[CH3:44]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 67208681N-((3-fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methyl)-6-(piperazin-1-yl)nicotinamide

Product 1

HCID 565990266-(4-acetylpiperazin-1-yl)-N-((3-fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-((3-fluoro-2′-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)methyl)-6-(piperazin-1-yl)nicotinamide 46-3 (35 mg, 0.076 mmol) and DIEA (27 μL, 0.155 mmol) in DCM (1.0 mL) was added acetyl chloride 46-4 (7 μL, 0.095 mmol). After 20 minutes stirring, the mixture was diluted with ethyl acetate, washed with water, and dried over Na2SO4. After evaporation of the solvents followed by preparative reverse phase HPLC separation gave 6-(4-acetylpiperazin-1-yl)-N-((3-fluoro-2′-(trifluoromethyl)-[2,4′-bipyridin]-5-yl)methyl)nicotinamide as a solid 46. MS m/z 503.2 (M+1). 1H NMR 400 MHz (CDCl3) δ 8.76 (d, 1H), 8.58 (d, 1H), 8.54-8.50 (m, 1H), 8.29 (bs, 1H), 8.07 (d, 1H), 7.97 (dd, 1H), 7.60 (dd, 1H), 6.62 (d, 1H), 4.63 (s, 2H), 3.72-3.65 (m, 4H), 3.61-3.55 (m, 4H), 2.10 (s, 3H).

Workup

  1. washwashed with water
  2. dry with materialdried over Na2SO4
  3. customAfter evaporation of the solvents
  4. customfollowed by preparative reverse phase HPLC separation

Sources & evidence

ORD record
ord-48e0fdf73c734dca90ae7c0a5fbce75d
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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