Benzylamine → 6-(4-((Benzylamino)methyl)phenoxy)nicotinamide

HRID 228196Notes

Reaction equation

HRID 228196 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.[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[BH4-].[Na+]>CO>[CH2:19]([NH:26][CH2:1][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)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 4311764Sodium borohydrideHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide

Product 1

HCID 444349496-(4-((Benzylamino)methyl)phenoxy)nicotinamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-(4-Formyl-phenoxy)-nicotinamide (0.097 g, 0.4 mmol) in 5 mL of methanol with benzylamine (0.4 mmol), and 1 g of 3 Å molecular sieves. Stir for 18 h. Add sodium borohydride (0.076 g, 2 mmol), and stir for 18 h. Flush the reactions down through a 5 g SCX column, first wash with 1:1 chloroform/methanol, then collect washes with 1:1 chloroform/2 M ammonia in methanol. Adsorb the collected material on silica, then purify via a ISCO® Combiflash 16x system (use a 10 g silica cartridge, and elute with 98:2:2 chloroform/ethanol/ammonium hydroxide, gradient to 90:10:1 chloroform/ethanol/ammonium hydroxide). 1H NMR (DMSO-d6): 8.58 (d, 1H), 8.22 (m, 1H), 8.0 (s, 1H), 7.46 (s, 1H), 7.27-7.38 (m, 6H), 7.20 (m, 1H), 7.02-7.08 (m, 3H), 3.67-3.68 (d, 4H). TLC Rf (90:10:1 chloroform/ethanol/ammonium hydroxide): 0.31.

Workup

  1. customFlush the reactions down through a 5 g SCX column
  2. washfirst wash with 1:1 chloroform/methanol
  3. custompurify via a ISCO® Combiflash 16x system (
  4. washelute with 98:2:2 chloroform/ethanol/ammonium hydroxide, gradient to 90:10:1 chloroform/ethanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-c39938f09a4449fbace4c02914a95ac1
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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