Pentylamine → 5-(2-Fluoro-4-pentylaminomethylphenoxy)pyridine-2-carboxamide

HRID 130841Notes

Reaction equation

HRID 130841 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1.[CH2:20]([NH2:25])[CH2:21][CH2:22][CH2:23][CH3:24].[BH4-].[Na+]>CO>[F:1][C:2]1[CH:17]=[C:16]([CH2:18][NH:25][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 8060PentylamineHCID 4311764Sodium borohydrideHCID 597299375-(2-Fluoro-4-formylphenoxy)pyridine-2-carboxamide

Product 1

HCID 597302245-(2-Fluoro-4-pentylaminomethylphenoxy)pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.040 g, 0.154 mmol) amylamine (0.0139 g, 0.154 mmol) and 3 Å molecular sieves in a vial. Add methanol (1.5 mL), cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load directly onto a 5 g SCX column. Wash with methanol (10 mL), then elute with 2.0 M NH3 in methanol. Purify by loading the product onto a 5 g loading cartridge and eluting through a 10 g ISCO® column with 50% ethyl acetate, 5% (2.0 M NH3 in methanol) and 45% hexanes to give the title compound (0.0387 g, 76.0%: TOF MS ES+ 332.2 (M+H)+, HRMS calcd for C18H23N3O2F 332.1774 (M+H)+, found 332.1765, time 0.39 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=6.9 min, 100% purity.

Workup

  1. washWash with methanol (10 mL)
  2. washelute with 2.0 M NH3 in methanol
  3. customPurify
  4. washeluting through a 10 g ISCO® column with 50% ethyl acetate, 5% (2.0 M NH3 in methanol) and 45% hexanes

Sources & evidence

ORD record
ord-7caad0863dae4a6e80d1df9a8582fdf3
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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