p-Fluorophenethylamine → 5-(4-{[2-(4-Fluorophenyl)ethylamino]methyl}phenoxy)pyridine-2-carboxamide

HRID 228284

Reaction equation

HRID 228284 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[CH:5][CH:4]=1)=O.[F:19][C:20]1[CH:28]=[CH:27][C:23]([CH2:24][CH2:25][NH2:26])=[CH:22][CH:21]=1.[BH4-].[Na+]>CO>[F:19][C:20]1[CH:28]=[CH:27][C:23]([CH2:24][CH2:25][NH:26][CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[CH:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=3)=[CH:5][CH:4]=2)=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 4653p-FluorophenethylamineHCID 4311764Sodium borohydrideHCID 597301445-(4-Formylphenoxy)pyridine-2-carboxamide

Product 1

HCID 597299995-(4-{[2-(4-Fluorophenyl)ethylamino]methyl}phenoxy)pyridine-2-carboxamideYield 90.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Suspend 5-(4-formylphenoxy)pyridine-2-carboxamide (0.0271 g, 0.112 mmol) In methanol (2.1 mL). Add 4-fluorophenethylamine (0.015 mL, 0.112 mmol) and 3 Å molecular sieves. Stir at room temperature overnight. Add NaBH4 (in small excess) and stir for additional 3 hours. Load the reaction mixture directly onto a 5 g SCX column. Wash the column with methanol and elute with 2.0 M NH3 in methanol. Purify by flash chromatography, eluting with 70% ethyl acetate, 5% (2.0 M NH3 in methanol) and 25% hexanes to give the title compound (0.0370 g, 90.5%): TOF MS ES+ 366.2 (M+H)+, base peak TOF MS ES+ 227.1 (M-NHCH2CH2C6H4F)+, HRMS calcd for C21H21N3O2F 366.1618 (M+H)+, found 366.1621, time 0.42 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95°/over 19 min], tR=10.2 min, 100% purity.

Workup

  1. washWash the column with methanol
  2. washelute with 2.0 M NH3 in methanol
  3. customPurify by flash chromatography
  4. washeluting with 70% ethyl acetate, 5% (2.0 M NH3 in methanol) and 25% hexanes

Sources & evidence

ORD record
ord-4292ac42167a487faded6915d1aa1c2f
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Linked notes

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