Sodium borohydride → 5-{4-[(2-Cyclopentylethylamino)methyl]-2-fluorophenoxy}pyridine-2-carboxamide

HRID 492599Notes

Reaction equation

HRID 492599 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1.[CH:20]1([CH2:25][CH2:26][NH2:27])[CH2:24][CH2:23][CH2:22][CH2:21]1.[BH4-].[Na+]>CO>[CH:20]1([CH2:25][CH2:26][NH:27][CH2:18][C:16]2[CH:15]=[CH:14][C:3]([O:4][C:5]3[CH:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=3)=[C:2]([F:1])[CH:17]=2)[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 53056502-CyclopentylethanamineHCID 597299375-(2-Fluoro-4-formylphenoxy)pyridine-2-carboxamide

Product 1

HCID 597301125-{4-[(2-Cyclopentylethylamino)methyl]-2-fluorophenoxy}pyridine-2-carboxamideYield 10%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 ml, 20-95% over 18], tR=11.8 min, 94.2% purity.

Workup

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate

Sources & evidence

ORD record
ord-41f35bfc8e29428796b5582f2be33f3c
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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