Sodium borohydride → 5-{4-[(3-Ethylpentylamino)methyl]-2-fluorophenoxy}pyridine-2-carboxamide

HRID 130990Notes

Reaction equation

HRID 130990 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.[CH2:20]([CH:22]([CH2:26][CH3:27])[CH2:23][CH2:24][NH2:25])[CH3:21].[BH4-].[Na+]>CO>[CH2:20]([CH:22]([CH2:26][CH3:27])[CH2:23][CH2:24][NH:25][CH2:18][C:16]1[CH:15]=[CH:14][C:3]([O:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=2)=[C:2]([F:1])[CH:17]=1)[CH3:21]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 157055453-Ethylpentan-1-amineHCID 597299375-(2-Fluoro-4-formylphenoxy)pyridine-2-carboxamide

Product 1

HCID 597301385-{4-[(3-Ethylpentylamino)methyl]-2-fluorophenoxy}pyridine-2-carboxamideYield 58%

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), 3-ethylpentylamine (Example 733, Part B) (0.317 g, 2.75 mmol) and 3 {acute over (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 NH3 in methanol) in ethyl acetate to give the title compound (0.516 g, 58%): TOF MS ES+ 360.2 (M+H)+, HRMS calcd for C20H27N3O2F 360.2087 (M+H)+, found 360.2086, time 0.53 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 min, 20-95% over 18], tR=12.3 min, 100% 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 NH3 in methanol) in ethyl acetate

Sources & evidence

ORD record
ord-a636ad170a644ee582bffb5cecb8c34c
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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