Hydrochloric Acid → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[isobutyl(methyl)amino]methyl}-5-methylbenzamide Hydrochloride

HRID 14135

반응식

HRID 14135 반응식
[CH2:1]([N:5]([CH2:7][C:8]1[CH:9]=[C:10]([CH:14]=[C:15]([CH3:17])[CH:16]=1)[C:11]([OH:13])=O)[CH3:6])[CH:2]([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[NH2:61][C@@H:62]([CH2:76][C:77]1[CH:82]=[C:81]([F:83])[CH:80]=[C:79]([F:84])[CH:78]=1)[C@H:63]([OH:75])[CH2:64][NH:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[CH:68]=1.[ClH:85]>C(Cl)Cl.CO.C(OCC)C>[ClH:85].[F:83][C:81]1[CH:82]=[C:77]([CH:78]=[C:79]([F:84])[CH:80]=1)[CH2:76][C@H:62]([NH:61][C:11](=[O:13])[C:10]1[CH:14]=[C:15]([CH3:17])[CH:16]=[C:8]([CH2:7][N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH3:6])[CH:9]=1)[C@H:63]([OH:75])[CH2:64][NH:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[CH:68]=1

참가 물질

10

반응물 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210858333-{[Isobutyl(methyl)amino]methyl}-5-methylbenzoic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

생성물 1

HCID 68608329N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[isobutyl(methyl)amino]methyl}-5-methylbenzamide Hydrochloride

시약·촉매·용매 3

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매2회

실험 절차

To a stirred solution of 3-{[isobutyl(methyl)amino]methyl}-5-methylbenzoic acid (110 mg, 0.48 mmol) in methylene chloride (3 mL) is added HBTU (273 mg, 0.72 mmol), HOBt (97 mg, 0.72 mmol), and N,N -diisopropylethylamine (0.243 mL, 1.44 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (196 mg, 0.48 mmol), and the reaction mixture is stirred for 12 h at room temperature. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 10% methanol/chloroform) affords a clear oil, which is dissolved in methanol (2 mL). To this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol), and the reaction mixture is stirred for 1 h at room temperature. The reaction mixture is then diluted with ethyl ether (10 mL). The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 552.5 [M+H]+.

후처리

  1. washwashed with water, and saturated sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 10% methanol/chloroform)
  6. customaffords a clear oil, which
  7. stirringthe reaction mixture is stirred for 1 h at room temperature
  8. customThe precipitate that is formed
  9. filtrationis collected by filtration

출처 및 근거

ORD 기록
ord-d0a270bbcf054ecdb404ad665e776e68
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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