Isoamylamine → 6-{2-Methoxy-4-[(3-methylbutylamino)methyl]phenoxy}pyridazine-3-carboxamide

HRID 228433Notes

Reaction equation

HRID 228433 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:13]=[N:12][C:11]([C:14]([NH2:16])=[O:15])=[CH:10][CH:9]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[CH2:21]([NH2:26])[CH2:22][CH:23]([CH3:25])[CH3:24].[BH4-].[Na+]>CO>[CH3:20][O:19][C:5]1[CH:4]=[C:3]([CH2:1][NH:26][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:18]=[CH:17][C:6]=1[O:7][C:8]1[N:13]=[N:12][C:11]([C:14]([NH2:16])=[O:15])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 7894IsoamylamineHCID 4311764Sodium borohydrideHCID 597300016-(4-Formyl-2-methoxyphenoxy)pyridazine-3-carboxamide

Product 1

HCID 597302686-{2-Methoxy-4-[(3-methylbutylamino)methyl]phenoxy}pyridazine-3-carboxamideYield 44.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Place 6-(4-formyl-2-methoxyphenoxy)pyridazine-3-carboxamide (Example 721, Part C) (0.200 g, 0.732 mmol), isoamylamine (0.0670 g, 0.769 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.6 mL), cap and stir overnight. Add NaBH4 (ca. 3-5 eq in two portions) 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 10% to 20% (2.0 M NH3 in methanol) in ethyl acetate. Concentrate the fractions containing the product. Take the solid up in ethyl acetate (50 mL) and wash with 1.0 N NaOH (2×10 mL). Dry the organic layer over Na2SO4, filter and concentrate to give the title compound (0.112 g, 44%): TOF MS ES+ 345.2 (M+H)+, HRMS calcd for C18H25N4O3 345.1927 (M+H)+, found 345.1926, time 0.52 min; Anal. Calcd for C18H24N4O3: C, 62.77; H, 7.02; N, 16.27. Found: C, 62.29; H, 7.01; N, 15.50.

Workup

  1. customDry the column in a vacuum oven at room temperature
  2. customPurify
  3. washby eluting through a 40 g ISCO® column with 10% to 20% (2.0 M NH3 in methanol) in ethyl acetate
  4. concentrationConcentrate the fractions
  5. additioncontaining the product
  6. washwash with 1.0 N NaOH (2×10 mL)
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-15614520be0c4284a2017e8e9f0768fc
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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