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

HRID 2168783ノート

反応式

HRID 2168783 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b308f5df68104412b8bb02e2a353e187
出典データセット
uspto-grants-2015_06
特許番号
US09045461B2

反応ノート

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