2-Methoxybenzaldehyde → 6-{4-[2-(2-Methoxy-benzylamino)-ethyl]-phenoxy}-nicotinamide

HRID 228152

Reaction equation

HRID 228152 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:19]=[CH:18][C:7]([O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=2)=[CH:6][CH:5]=1.[CH3:20][O:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH:24]=O.[BH4-].[Na+]>CO>[CH3:20][O:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH2:24][NH:1][CH2:2][CH2:3][C:4]1[CH:19]=[CH:18][C:7]([O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 86582-MethoxybenzaldehydeHCID 4311764Sodium borohydrideHCID 597300176-[4-(2-Amino-ethyl)-phenoxy]-nicotinamide

Product 1

HCID 597303966-{4-[2-(2-Methoxy-benzylamino)-ethyl]-phenoxy}-nicotinamideYield 85.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add three-angstrom molecular sieves to a stirred solution of 6-[4-(2-amino-ethyl)-phenoxy]-nicotinamide (0.1000 g, 0.3887 mmol) (compound of example 33), 2-methoxybenzaldehyde (0.047 mL, 0.39 mmol), and methanol (5 mL). Agitate the reaction for 18 h on a platform shaker at room temperature. Add sodium borohydride and agitate for 1 h at room temperature. Filter to remove the molecular sieves and load the reaction mixture directly onto a 10 g prepacked SCX cartridge. Flush with methanol (150 mL) and elute the product off the SCX cartridge with 2 M ammonia in methanol (50 mL). Concentrate on a rotary evaporator to give 0.1253 g (85%) of 6-{4-[2-(2-methoxy-benzylamino)-ethyl]-phenoxy}-nicotinamide: HPLC (30/70 to 90/10 ACN/(0.1% TFA in water) Zorbax SB-Phenyl Column 4.6 mm×15 cm×5 micron: Retention time: 4.14 minutes, Purity: 97.9%; mass spectrum (ion spray): m/z=378.1 (M+1).

Workup

  1. customthe reaction for 18 h on a platform shaker at room temperature
  2. filtrationFilter
  3. customto remove the molecular sieves and load the reaction mixture directly onto a 10 g prepacked SCX cartridge
  4. customFlush with methanol (150 mL)
  5. washelute the product off the SCX cartridge with 2 M ammonia in methanol (50 mL)
  6. concentrationConcentrate on a rotary evaporator

Sources & evidence

ORD record
ord-b3acef7e9e4a4039970a72a40a2eb3ff
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Linked notes

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