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Hydrochloric Acid → 4-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1-(methylsulfonyl)-1,2,3,4-tetrahydroquinoxaline-6-carboxamide

HRID 14203
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HRID 14203 반응식
[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([OH:17])=O)[CH:13]=2)[N:8]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].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.[NH2:65][C@@H:66]([CH2:80][C:81]1[CH:86]=[C:85]([F:87])[CH:84]=[C:83]([F:88])[CH:82]=1)[C@H:67]([OH:79])[CH2:68][NH:69][CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[C:73]([CH2:77][CH3:78])[CH:72]=1.Cl>C(Cl)Cl.CO>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([NH:65][C@@H:66]([CH2:80][C:81]3[CH:82]=[C:83]([F:88])[CH:84]=[C:85]([F:87])[CH:86]=3)[C@H:67]([OH:79])[CH2:68][NH:69][CH2:70][C:71]3[CH:76]=[CH:75][CH:74]=[C:73]([CH2:77][CH3:78])[CH:72]=3)=[O:17])[CH:13]=2)[N:8]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
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참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 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 210859284-Butyl-1-(methylsulfonyl)-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid
HCID 57487282
(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

생성물 1

HCID 575120614-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1-(methylsulfonyl)-1,2,3,4-tetrahydroquinoxaline-6-carboxamide수율 45.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매3회

실험 절차

A solution of 4-butyl-1-(methylsulfonyl)-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (99 mg), HATU (181 mg), HOBt (64 mg), and diisopropylethylamine (100 μL) was stirred in methylene chloride (1.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (129 mg) and diisopropylethylamine (100 μL) in methylene chloride (1.0 mL) was added and the mixture was stirred overnight. The mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine. The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (1 mL), and treated with hydrochloric acid (0.5 mL, 1.0 M diethyl ether). The resulting precipitate was collected by filtration to provide 90 mg of the title compound: ESI MS m/z 629 [M+H]+.

후처리

  1. washwashed with 1 N hydrochloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine
  2. dry with materialThe organic layer was then dried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)
  6. customprovided a clear solid
  7. filtrationThe resulting precipitate was collected by filtration

출처 및 근거

ORD 기록
ord-fbe6f2ace36b4d5c9cfc241123abe1c2
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07727997B2

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