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

HRID 14309

反応式

HRID 14309 の反応式
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

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-23abda02078c49c7a833d7427136e1af
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

関連ノート

読み込み中…