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

HRID 1972061Notes

Reaction equation

HRID 1972061 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([CH2:14][N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])(C)(C)C.Cl.FC1C(OC([C:29]2[N:30]=[N:31][C:32]([CH2:48][CH2:49][CH2:50][CH3:51])=[C:33]([C:35]3[CH:40]=[CH:39][C:38]([O:41][CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)=[CH:37][CH:36]=3)[CH:34]=2)=O)=C(F)C(F)=C(F)C=1F>C(Cl)Cl.O1CCOCC1.C(OCC)(=O)C>[N:15]([CH2:14][C@@H:10]1[O:11][CH2:12][CH2:13][N:8]([C:6]([C:29]2[N:30]=[N:31][C:32]([CH2:48][CH2:49][CH2:50][CH3:51])=[C:33]([C:35]3[CH:36]=[CH:37][C:38]([O:41][CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)=[CH:39][CH:40]=3)[CH:34]=2)=[O:7])[CH2:9]1)=[N+:16]=[N-:17]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 57686784(R)-2-azidomethyl-morpholine-4-carboxylic acid tert-butyl esterHCID 866578236-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester

Product 1

HCID 86657825((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanoneYield 105.8%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (R)-2-azidomethyl-morpholine-4-carboxylic acid tert-butyl ester (0.82 mmol, 0.2 g) in DCM (2 mL) was added 4 N HCl in dioxane (4 mL) and continued stirring at ambient temperature for 45 min. The volatiles were removed under reduced pressure, and the residue was dissolved in NMP (4 mL). To this was added 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester (Example 93, 0.77 mmol, 0.4 g) followed by TEA (0.5 mL) and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water, followed by saturated sodium bicarbonate. The organic layer was dried, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography using ethyl 30% acetate in hexanes to provide ((R)-2-azidomethyl-morpholin-4-yl)-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yl]-methanone (0.39 g).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionthe residue was dissolved in NMP (4 mL)
  3. stirringthe reaction mixture was stirred at room temperature for 30 min
  4. washwashed with water
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-efa9d0b2de1c4dd99c8ff6d628a5977f
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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