Triethylamine → 6-{4-[4-(4-Fluoro-phenyl)-piperazin-1-ylmethyl]-phenoxy}-nicotinamide

HRID 492372Notes

Reaction equation

HRID 492372 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=2)=[CH:5][CH:4]=1)=O.Cl.Cl.[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C(N(CC)CC)C.[BH4-].[Na+]>CO>[F:21][C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH2:33][CH2:32][N:31]([CH2:1][C:3]3[CH:18]=[CH:17][C:6]([O:7][C:8]4[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=4)=[CH:5][CH:4]=3)[CH2:30][CH2:29]2)=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 162119161-(4-Fluorophenyl)piperazine dihydrochlorideHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide2×

Product 1

HCID 597303356-{4-[4-(4-Fluoro-phenyl)-piperazin-1-ylmethyl]-phenoxy}-nicotinamideYield 21.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-(4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.299 g, 1.23 mmol), 1-(4-fluoro-phenyl)-piperizine, bis hydrochloride salt (0.314 g, 1.24 mmol), triethylamine (0.36 mL, 2.58 mmol) in methanol (12 mL) and stir. After 23 h, add sodium borohydride (0.108 g, 2.85 mmol). After 1 d, concentrate and purify the residue by silica gel chromatography (25:1→4:1 methylene chloride:methanol) to provide 0.107 g (21%) of the title compound as a white solid: high resolution mass spectrum (electrospray): m/z calc for C23H24FN4O2 407.1883, found 407.1883; 1H NMR (methanol-d4): 8.67 (d, 1H, J=2.4 Hz), 8.30 (dd, 1H, J=2.4; 8.8 Hz), 7.52-7.47 (m, 2H), 7.20-7.15 (m, 2H), 7.05 (d, 1H, J=7.8 Hz), 7.01 (d, 1H, J=6.3 Hz), 3.66 (s, 2H), 3.21-3.16 (m, 4H), 2.74-2.68 (m, 4H).

Workup

  1. waitAfter 1 d
  2. concentrationconcentrate
  3. custompurify the residue by silica gel chromatography (25:1→4:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-9003bcc0f0e34267b5706b48398e6b36
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

Loading…