Isohexylamine → 6-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamide

HRID 228322Notes

Reaction equation

HRID 228322 reaction equation
CS(O)(=O)=O.[CH3:6][O:7][C:8]1[CH:23]=[C:22]([CH2:24][NH:25][CH2:26][CH2:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:21]=[CH:20][C:9]=1[O:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=1.C(C1C=CC(OC2C=CC(C(N)=O)=CN=2)=C(OC)C=1)=O.CC(C)CCCN.[BH4-].[Na+]>CO>[CH3:6][O:7][C:8]1[CH:23]=[C:22]([CH2:24][NH:25][CH2:26][CH2:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:21]=[CH:20][C:9]=1[O:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=1

Participants

6

Reactant 4

HCID 219608IsohexylamineHCID 4311764Sodium borohydrideHCID 597300166-(4-Formyl-2-methoxyphenoxy)nicotinamideHCID 866081356-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamide methanesulfonate

Product 1

HCID 597301166-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamideYield 71.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Part B: 6-{2-Methoxy-4-[(4-methylpentylamino)methyl]phenoxy}nicotinamide methanesulfonate Place 6-(4-formyl-2-methoxyphenoxy)nicotinamide (Example 414, Part B) (0.100 g, 0.367 mmol), 4-methylpentylamine (Part A, 0.0409 g, 0.404 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.6 mL), cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 5 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol) in ethyl acetate to give 6-{2-methoxy-4-[(4-methylpentylamino)methyl]phenoxyl}nicotinamide (0.131 g, 71.8%). Dissolve the compound in dichloromethane (2.5 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 (0.124 g, 100%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H28N3O3 358.2131 (M+H)+, found 358.2119, time 0.39 mine HPLC [Waters XTerra™ MS C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 15 min], tR=8.2 min, 100% purity.

Workup

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol) in ethyl acetate

Sources & evidence

ORD record
ord-e66edca568d844ab8caf04bd446f2594
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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