Hydrochloric Acid → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]piperidine-1-carboxamide

HRID 14309

반응식

HRID 14309 반응식
ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.[CH3:22][S:23]([CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35]C(C)(C)C)=O)[CH2:29][CH2:28]1)(=[O:25])=[O:24].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[NH2:54][C@@H:55]([CH2:69][C:70]1[CH:75]=[C:74]([F:76])[CH:73]=[C:72]([F:77])[CH:71]=1)[C@H:56]([OH:68])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([CH2:66][CH3:67])[CH:61]=1.Cl>C(Cl)Cl.CO.C(OCC)C>[F:76][C:74]1[CH:75]=[C:70]([CH:71]=[C:72]([F:77])[CH:73]=1)[CH2:69][C@H:55]([NH:54][C:33]([N:30]1[CH2:29][CH2:28][CH:27]([CH2:26][S:23]([CH3:22])(=[O:24])=[O:25])[CH2:32][CH2:31]1)=[O:35])[C@H:56]([OH:68])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([CH2:66][CH3:67])[CH:61]=1

참가 물질

10

반응물 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 21087275Tert-butyl 4-((methylsulfonyl)methyl)piperidine-1-carboxylateHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

생성물 1

HCID 68607620N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]piperidine-1-carboxamide수율 7.2%

시약·촉매·용매 3

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매3회

실험 절차

To an ice-cold, stirred solution of triphosgene (108 mg, 0.36 mmol) and diisopropylethylamine (0.6 mL, 3.3 mmol) in methylene chloride (2.0 mL) was added amino sulfone from step 4 (210 mg, 0.98 mmol) in methylene chloride (3.5 mL) dropwise. After 5 min a solution of dihydrochloride of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (401 mg, 0.98 mmol) was added and the reaction mixture was warmed until the solution became homogeneous. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and saturated sodium chloride, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 15:85 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (1 mL), and treated with hydrochloric acid (0.3 mL of a 1.0 M solution in diethyl ether, 0.3 mmol). The resulting precipitate was collected by filtration to provide the title compound (38 mg): mp 130-134° C.; APCI MS m/z 538 [M+H]+.

후처리

  1. temperaturethe reaction mixture was warmed until the solution
  2. washwashed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and saturated sodium chloride
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 15:85 methanol/chloroform)
  7. customprovided a clear solid
  8. filtrationThe resulting precipitate was collected by filtration

출처 및 근거

ORD 기록
ord-23abda02078c49c7a833d7427136e1af
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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