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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 348993
ノート
印刷プレビュー

反応式

HRID 348993 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2 回HCID 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

生成物 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-carboxamide収率 45.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

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 hydorchloric acid (10 mL), saturated sodium bicarbonate (10 mL), and brine. The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purificatio 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]+.

後処理

  1. washwashed with 1 N hydorchloric 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. customPurificatio by flash column chromatography (silica, 1:9 methanol/chloroform) provided a clear solid
  6. filtrationThe resulting precipitate was collected by filtration

出典と根拠

ORDレコード
ord-cca39f16f6d2442d986ff9c592e84355
出典データセット
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07176242B2

反応ノート

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