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

HRID 747554Notes

Reaction equation

HRID 747554 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][CH2:4][NH:5][CH2:6][C:7]1[CH:21]=[CH:20][C:10]([O:11][C:12]2[S:16][C:15]([C:17]([NH2:19])=[O:18])=[CH:14][CH:13]=2)=[CH:9][CH:8]=1.[O:23]1[CH2:28]CC(CCN)C[CH2:24]1.[BH4-].[Na+]>CO>[O:23]1[CH2:28][CH2:22][CH:2]([CH2:3][CH2:4][NH:5][CH2:6][C:7]2[CH:21]=[CH:20][C:10]([O:11][C:12]3[S:16][C:15]([C:17]([NH2:19])=[O:18])=[CH:14][CH:13]=3)=[CH:9][CH:8]=2)[CH2:1][CH2:24]1

Participants

5

Reactant 3

HCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 4311764Sodium borohydrideHCID 103138305-{4-[(3-Methylbutylamino)methyl]phenoxy}thiophene-2-carboxamide

Product 1

HCID 586773835-(4-{[2-(Tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(4-formylphenoxy)thiophene-2-carboxamide (Example 10, Part C) (0.235 g, 0.948 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.122 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 30% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes to give the title compound: TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C19H25N2O3S 361.1586 (M+H)+, found 361.1604, time 0.36 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=9.4 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 30% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes

Sources & evidence

ORD record
ord-2fe12e5e66ba4beba71fe08363f9e214
Source dataset
uspto-grants-2008_07
Patent number
US07396943B2

Reaction notes

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