2-(Oxan-4-yl)ethan-1-amine → 5-(2-Methoxy-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)pyridine-2-carboxamide

HRID 131007Notes

Reaction equation

HRID 131007 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)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[O:21]1[CH2:26][CH2:25][CH:24]([CH2:27][CH2:28][NH2:29])[CH2:23][CH2:22]1.[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:29][CH2:28][CH2:27][CH:24]2[CH2:25][CH2:26][O:21][CH2:22][CH2:23]2)[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 597302085-(4-Formyl-2-methoxyphenoxy)pyridine-2-carboxamide

Product 1

HCID 597303675-(2-Methoxy-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formyl-2-methoxyphenoxy)pyridine-2-carboxamide (Ex 391, Part A) (0.600 g, 2.20 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.285 g, 2.20 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (11.0 mL), cap and stir overnight. Add NaBH4 (0.0833 g, 2.20 mmol) and stir until the gasses stop evolving. Filter the reaction mixture, then concentrate it. Purify by chromatography eluting with 5% to 30% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes to give 5-(2-methoxy-4-{[2-(tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)pyridine-2-carboxamide. (0.6103 g, 71.9%). Dissolve the compound in dichloromethane:methanol (3.2 mL) and add 1 equivalent of 0.50 M methanesulfonic acid in dichloromethane. Stir the solution for a short time before concentrating to give the title compound (0.775 g): TOF MS ES+ 386.2 (M+H)+, HRMS calcd for C21H28N3O4 386.2080 (M+H)+, found 386.2078, time 0.39 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=9.3 min, 100% purity.

Workup

  1. filtrationFilter the reaction mixture
  2. concentrationconcentrate it
  3. customPurify by chromatography
  4. washeluting with 5% to 30% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes

Sources & evidence

ORD record
ord-0fae609fab384c2faf3d2b0d0fa2f350
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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