Pyridine → N-benzyl-2-(2-(3-((methyl(2-(piperazin-1-yl)ethyl)amino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

HRID 625345Notes

Reaction equation

HRID 625345 reaction equation
[CH3:1][N:2]([CH2:12][C:13]1[CH:14]=[C:15]([CH:51]=[CH:52][CH:53]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:21][C:20]=1[C:31]1[CH:32]=[C:33]([CH:48]=[CH:49][N:50]=1)[C:34]([NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40](C(F)(F)F)[CH:39]=1)=[O:35])=[O:17])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8](C)[CH2:7][CH2:6]1.C(OC(=O)C)(=O)C.N1C=CC=CC=1>O1CCCC1>[CH2:37]([NH:36][C:34](=[O:35])[C:33]1[CH:48]=[CH:49][N:50]=[C:31]([C:20]2[CH:21]=[C:22]([N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:23]=[CH:24][C:19]=2[NH:18][C:16](=[O:17])[C:15]2[CH:51]=[CH:52][CH:53]=[C:13]([CH2:12][N:2]([CH3:1])[CH2:3][CH2:4][N:5]3[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]3)[CH:14]=2)[CH:32]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 665868412-(2-(3-((Methyl(2-(4-methylpiperazin-1-yl)ethyl)amino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

Product 1

HCID 66586846N-benzyl-2-(2-(3-((methyl(2-(piperazin-1-yl)ethyl)amino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The free base of N-benzyl-2-(2-(3-((methyl(2-(piperazin-1-yl)ethyl)amino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide was prepared as described in the preparation of 2-(2-(3-((methyl(2-(4-methylpiperazin-1-yl)ethyl)amino)methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)-benzyl)isonicotinamide 40. Into a 50-mL round-bottom flask, was placed a solution of this free base (150 mg, 0.21 mmol, 1.00 equiv) in tetrahydrofuran (5 mL), acetyl acetate (26 mg, 0.25 mmol, 1.20 equiv), and pyridine (33 mg, 0.42 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 44 mg (17%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.25 (s, 1H), 9.56-9.52 (m, 1H), 8.93-8.91 (d, J=5.1 Hz, 1H), 8.33-8.26 (m, 2H), 8.04 (s, 1H), 7.96-7.93 (d, J=7.8 Hz, 1H), 7.85-7.83 (d, J=6.3 Hz, 1H), 7.70-7.55 (m, 6H), 7.29-7.26 (d, J=8.7 Hz, 1H), 4.64-4.62 (d, J=5.7 Hz, 2H), 4.29 (s, 2H), 3.54 (s, 4H), 3.30-3.21 (m, 6H), 3.03 (s, 2H), 2.80-2.73 (m, 3H), 2.66 (s, 3H), 1.99 (s, 3H), 1.73 (s, 4H), 1.60-1.59 (d, J=4.8 Hz, 1H). MS (ES, m/z): 756 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product (200 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-b5e6f3f2f7894f23a0a7d83cab10511c
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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