Isoamylamine → 5-{4-[(3-Methylbutylamino)methyl]phenoxy}thiophene-2-carboxamide

HRID 747552Notes

Reaction equation

HRID 747552 reaction equation
[CH:1]([C:3]1[CH:17]=[CH:16][C:6]([O:7][C:8]2[S:12][C:11]([C:13]([NH2:15])=[O:14])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1)=O.[CH2:18]([NH2:23])[CH2:19][CH:20]([CH3:22])[CH3:21].[BH4-].[Na+]>CO>[CH3:21][CH:20]([CH3:22])[CH2:19][CH2:18][NH:23][CH2:1][C:3]1[CH:17]=[CH:16][C:6]([O:7][C:8]2[S:12][C:11]([C:13]([NH2:15])=[O:14])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 7894IsoamylamineHCID 4311764Sodium borohydrideHCID 586773915-(4-Formylphenoxy)thiophene-2-carboxamide

Product 1

HCID 103138305-{4-[(3-Methylbutylamino)methyl]phenoxy}thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formylphenoxy)thiophene-2-carboxamide (0.235 g, 0.948 mmol), isoamylamine (0.087 g, 0.996 mmol) and 3 Å molecular sieves in a vial. Add methanol (4.7 mL), cap and stir overnight. Add NaBH4 (0.0359 g, 0.948 mmol) 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes to give the title compound: TOF MS ES+ 319.1 (M+H)+, HRMS calcd for C17H23N2O2S 319.1480 (M+H)+, found 319.1488, time 0.38 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=10.8 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 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes

Sources & evidence

ORD record
ord-e1aed406c10e4939bbc4d411e22e6d60
Source dataset
uspto-grants-2008_07
Patent number
US07396943B2

Reaction notes

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