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

HRID 1972061노트

반응식

HRID 1972061 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-efa9d0b2de1c4dd99c8ff6d628a5977f
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431575B2

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