((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone → ((S)-2-aminomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone

HRID 402056Notes

Reaction equation

HRID 402056 reaction equation
[N:1]([CH2:4][C@@H:5]1[O:10][CH2:9][CH2:8][N:7]([C:11]([C:13]2[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:21][CH:20]=3)[CH:18]=2)=[O:12])[CH2:6]1)=[N+]=[N-].[H][H]>C(OCC)(=O)C.[Pd]>[NH2:1][CH2:4][C@@H:5]1[O:10][CH2:9][CH2:8][N:7]([C:11]([C:13]2[N:14]=[N:15][C:16]([CH2:32][CH2:33][CH2:34][CH3:35])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:21][CH:20]=3)[CH:18]=2)=[O:12])[CH2:6]1

Participants

5

Reactant 2

HCID 86657825((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanoneHCID 178418361HCID 178418361, compound

Product 1

HCID 67373496((S)-2-aminomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanoneYield 91.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of ((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone (0.799 mmol, 0.39 g) in ethyl acetate (4 mL) was added 10% palladium on carbon (0.1 g, wet), and the resulting reaction mixture was subjected to catalytic hydrogenation using a balloon full of hydrogen for 3 h. The catalyst was filtered through a pad of celite, and the celite pad was washed with methanol. The combined filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography using ethyl acetate followed by 10% methanolic solution of ammonia (2 M ammonia in methanol) in ethyl acetate to provide ((S)-2-aminomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone (0.33 g) which was converted into dihydrochloride salt using 4 N HCl in dioxane. LCMS: m/z 452.8 [M+1]. 1H NMR (400 MHz, CD3OD) δ 8.12 and 8.13 (1H, s), 7.46 (2H, dd), 7.12 (2H, d), 4.42-4.66 (2H, m), 3.42-4.16 (5H, m), 2.91-3.25 (5H, m), 1.99 (2H, m), 1.83 (2H, m), 1.3-1.69 (10H, m), 0.85 (3H, t)

Workup

  1. customthe resulting reaction mixture
  2. customfor 3 h
  3. filtrationThe catalyst was filtered through a pad of celite
  4. washthe celite pad was washed with methanol
  5. concentrationThe combined filtrate was concentrated under reduced pressure
  6. customThe residue was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-acb5cef041b1405499b099f66651f2de
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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