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

HRID 14309

Reaktionsgleichung

Reaktionsgleichung von HRID 14309
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

Komponenten

10

Edukt 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

Produkt 1

HCID 68607620N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]piperidine-1-carboxamideAusbeute 7,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-23abda02078c49c7a833d7427136e1af
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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