1-Hydroxybenzotriazole → N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(5-methyl-1,2,4-oxadiazol-3-yl)-N3,N3-dipropylisophthalamide Hydrochloride

HRID 14061

반응식

HRID 14061 반응식
[CH2:1]([N:4]([CH2:22][CH2:23][CH3:24])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[N:20]=[C:19]([CH3:21])[O:18][N:17]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.[ClH:68].Cl.[NH2:70][C@@H:71]([CH2:85][C:86]1[CH:91]=[C:90]([F:92])[CH:89]=[C:88]([F:93])[CH:87]=1)[C@H:72]([OH:84])[CH2:73][NH:74][CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[C:78]([CH2:82][CH3:83])[CH:77]=1>C(Cl)Cl>[ClH:68].[F:92][C:90]1[CH:91]=[C:86]([CH:87]=[C:88]([F:93])[CH:89]=1)[CH2:85][C@H:71]([NH:70][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([C:16]2[N:20]=[C:19]([CH3:21])[O:18][N:17]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:22][CH2:23][CH3:24])=[O:6])[CH:8]=1)[C@H:72]([OH:84])[CH2:73][NH:74][CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[C:78]([CH2:82][CH3:83])[CH:77]=1

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2회HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210857883-[(Dipropylamino)carbonyl]-5-(5-methyl-1,2,4-oxadiazol-3-yl)benzoic AcidHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

생성물 1

HCID 68607417N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(5-methyl-1,2,4-oxadiazol-3-yl)-N3,N3-dipropylisophthalamide Hydrochloride

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

A solution of 3-[(dipropylamino)carbonyl]-5-(5-methyl-1,2,4-oxadiazol-3-yl)benzoic acid (209 mg, 0.63 mmol), HATU (359 mg, 0.95 mmol), HOBt (128 mg, 0.95 mmol), and diisopropylethylamine (165 μL, 0.95 mmol) is stirred in methylene chloride (2.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in Example SP-272 (257 mg, 0.63 mmol) and diisopropylethylamine (165 μL, 0.95 mmol) in methylene chloride (2.0 mL) is added and the reaction mixture is stirred overnight. The reaction mixture is diluted with methylene chloride, washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provides the title compound as the free base. The solid is 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 is collected by filtration to provide the title compound. APCI MS m/z 648.4 [M+H]+.

후처리

  1. additionis added
  2. washwashed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and brine
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

출처 및 근거

ORD 기록
ord-850f8369adcb4fd8b5fa402985e7cbc3
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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