Bupropion → 2-[(4-(3-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

HRID 2357743노트

반응식

HRID 2357743 반응식
[CH3:1][CH:2]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([Cl:11])[CH:10]=1)=[O:4].Cl.ClC1C=C(C(=O)C(NC(C)(C)C)C)C=CC=1.C(N(CC)CC)C.[NH2:41][S:42]([C:45]1[C:46]([Cl:74])=[CH:47][C:48]([NH:67][CH2:68][C:69]2[O:70][CH:71]=[CH:72][CH:73]=2)=[C:49]([CH:66]=1)[C:50]([O:52][CH2:53][CH2:54][CH2:55][O:56][C:57](=[O:65])[CH2:58][CH2:59][C:60]([O:62][CH2:63]Cl)=[O:61])=[O:51])(=[O:44])=[O:43]>C(#N)C>[NH2:41][S:42]([C:45]1[C:46]([Cl:74])=[CH:47][C:48]([NH:67][CH2:68][C:69]2[O:70][CH:71]=[CH:72][CH:73]=2)=[C:49]([CH:66]=1)[C:50]([O:52][CH2:53][CH2:54][CH2:55][O:56][C:57](=[O:65])[CH2:58][CH2:59][C:60]([O:62][CH2:63][N:12]([C:13]([CH3:15])([CH3:14])[CH3:16])[CH:2]([CH3:1])[C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([Cl:11])[CH:10]=1)=[O:4])=[O:61])=[O:51])(=[O:43])=[O:44]

참가 물질

6

반응물 4

HCID 444BupropionHCID 8471TriethylamineHCID 62884Bupropion HydrochlorideHCID 68457545Chloromethyl 4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoate

생성물 1

HCID 684542782-[(4-(3-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

A solution of bupropion[1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride (700), (U.S. Pat. No. 3,819,706 and U.S. Pat. No. 3,885,046) (0.025 mole), triethylamine (0.055 mole) and acetonitrile (30 mL) is stirred with cooling on an ice bath. A solution of chloromethyl 4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoate (0.025 mole) in acetonitrile (30 mL) is added dropwise. After the addition is complete, the reaction is heated to reflux for 2 hours. The reaction is cooled, the volatiles removed by spin evaporation, and the residue partitioned between dichloromethane and 5% aqueous sodium bicarbonate. The organic layer is washed with water, and then with a saturated sodium chloride solution. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give a solid that may be recrystallized to give 2-[(4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone (920). See eg., U.S. Pat. No. 5,104,870 and Sandler, et al., Organic Functional Group Preparations, p. 324 (1968).

후처리

  1. temperaturewith cooling on an ice bath
  2. additionAfter the addition
  3. temperaturethe reaction is heated
  4. temperatureto reflux for 2 hours
  5. temperatureThe reaction is cooled
  6. customthe volatiles removed by spin evaporation
  7. customthe residue partitioned between dichloromethane and 5% aqueous sodium bicarbonate
  8. washThe organic layer is washed with water
  9. dry with materialThe organic layer is dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give crude product, which
  13. custommay be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent
  14. customspin evaporated in vacuo
  15. customto give a solid
  16. customthat may be recrystallized

출처 및 근거

ORD 기록
ord-dd5300488f5c4c5ab75196dd9aa1c016
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07763612B2

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