Triethylamine → (+/-)-6-[4-(2-Phenyl-piperidin-ylmethyl)-phenoxy]-nicotinamide

HRID 492377Notes

Reaction equation

HRID 492377 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.[C:20]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][NH:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C.[BH4-].[Na+]>CO>[C:20]1([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[CH:5][CH:4]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 178142742-phenylpiperidineHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide2×

Product 1

HCID 59730347(+/-)-6-[4-(2-Phenyl-piperidin-ylmethyl)-phenoxy]-nicotinamideYield 2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-(4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.152 g, 0.628 mmol), 2-phenyl-piperidine hydrochloride salt (0.122 g, 0.620 mmol), triethylamine (0.178 mL, 1.28 mmol) in methanol (6.0 mL) and stir. After 21 hours, add sodium borohydride (0.108 g, 2.85 mmol). After about 24 hours, concentrate and purify the residue by silica gel chromatography (25:1→4:1 methylene chloride:methanol) then reverse-phase HPLC to provide 0.0047 g (2%) of the title compound as a white solid: mass spectrum (electrospray): m/z=388.2 (M+1); 1H NMR (methanol-d4): 8.66 (d, 1H, J=2.4 Hz), 8.29 (dd, 1H, J=2.4, 8.3 Hz), 7.52 (d, 2H, J=7.3 Hz), 7.41 (t, 2H, J=7.3 Hz), 7.37-7.28 (m, 3H), 7.11 (d, 2H, J=8.3 Hz), 7.02 (d, 1H, J=8.8 Hz), 3.81 (d, 1H, J=10.7 Hz), 3.39 (s, 2H), 3.20-2.94 (m, 2H), 2.17 (s br, 1H), 1.93-1.61 (m, 4H), 1.59-1.44 (m, 1H).

Workup

  1. waitAfter about 24 hours
  2. concentrationconcentrate
  3. custompurify the residue by silica gel chromatography (25:1→4:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-12ab187fcd6c487aa9c26fcdc0b310c4
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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