Dichloromethane → 2-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,2,3,4-tetrahydroisoquinoline-7-carboxamide Dihydrochloride

HRID 14106

Reaktionsgleichung

Reaktionsgleichung von HRID 14106
[CH2:1]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([C:15]([OH:17])=O)=[CH:10][CH:11]=2)[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.[NH2:61][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.C(Cl)[Cl:86]>>[ClH:86].[ClH:86].[CH2:1]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([C:15]([NH:61][C@@H:62]([CH2:76][C:77]3[CH:78]=[C:79]([F:84])[CH:80]=[C:81]([F:83])[CH:82]=3)[C@H:63]([OH:75])[CH2:64][NH:65][CH2:66][C:67]3[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[CH:68]=3)=[O:17])=[CH:10][CH:11]=2)[CH2:6]1)[CH2:2][CH2:3][CH3:4]

Komponenten

7

Edukt 6

HCID 6344Dichloromethane3×HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210854282-Butyl-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Produkt 1

HCID 686085232-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1,2,3,4-tetrahydroisoquinoline-7-carboxamide Dihydrochloride

Versuchsvorschrift

A solution of 2-butyl-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (190 mg, 0.81 mmol), HATU (465 mg, 1.2 mmol), HOBt (162 mg, 1.2 mmol), and diisopropylethylamine (250 μL, 1.6 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 prepared by the method in Example SP-272 (332 mg, 0.81 mmol) and diisopropylethylamine (250 μL, 1.6 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 (15 mL), saturated sodium bicarbonate (15 mL), and brine. The organic layer is then 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 (0.2 mL, 1.0 M diethyl ether, 0.2 mmol). The resulting precipitate was collected by filtration to provide the title compound. ESI MS m/z 550.3 [M+H]+.

Aufarbeitung

  1. additionis added
  2. washwashed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine
  3. dry with materialThe organic layer is then dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-ed3bc5cd608d42b5a5bc11ceded44e33
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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