Sodium borohydride → 6-{4-[(2-Cyclopentyl-ethylamino)-methyl]-phenoxy}-nicotinamide

HRID 228197Notes

Reaction equation

HRID 228197 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.[CH:19]1([CH2:24][CH2:25][NH2:26])[CH2:23][CH2:22][CH2:21][CH2:20]1.[BH4-].[Na+]>CO>[CH:19]1([CH2:24][CH2:25][NH:26][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)[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 53056502-CyclopentylethanamineHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide

Product 1

HCID 597302616-{4-[(2-Cyclopentyl-ethylamino)-methyl]-phenoxy}-nicotinamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-(4-formyl-phenoxy)-nicotinamide (0.61 g, 2.54 mmol) with 2-Cyclopentyl-ethylamine (0.38 g, 3.3 mmol), 2 g of 3 Å molecular sieves, and 10 mL of methanol. Stir for 18 h under nitrogen. Add sodium borohydride (0.5 g, 13.2 mmol), and stir for 24 h. Filter through Celite, remove the solvent in vacuo. Partition the residue between water (50 mL) and ethyl acetate (100 mL). Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide) to afford 0.45 g of product. HPLC retention time: 5.93 min (98.7% purity), ESMS (M+): 340.

Workup

  1. filtrationFilter through Celite
  2. customremove the solvent in vacuo
  3. customPartition the residue between water (50 mL) and ethyl acetate (100 mL)
  4. dry with materialDry the organic phase (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customAdsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-d8f33de4ee394fc48ecfff8cfc40774b
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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