Diisopropylethylamine → N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N3,N3-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide

HRID 14087

Reaktionsgleichung

Reaktionsgleichung von HRID 14087
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10](O)=[O:11])=[O:6])[CH2:2][CH3:3].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:59][C@@H:60]([CH2:75][C:76]1[CH:81]=[C:80]([F:82])[CH:79]=[C:78]([F:83])[CH:77]=1)[C@H:61]([OH:74])[CH2:62][NH:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([CH:71]([CH3:73])[CH3:72])[CH:66]=1>CN(C=O)C>[F:82][C:80]1[CH:81]=[C:76]([CH:77]=[C:78]([F:83])[CH:79]=1)[CH2:75][C@H:60]([NH:59][C:10](=[O:11])[C:9]1[CH:13]=[C:14]([C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:21][CH2:22][CH3:23])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)[C@H:61]([OH:74])[CH2:62][NH:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([CH:71]([CH3:73])[CH3:72])[CH:66]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210857833-[(Dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoic AcidHCID 57487288(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-isopropylbenzyl)amino]butan-2-ol Dihydrochloride

Produkt 1

HCID 58802278N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-2-hydroxy-3-[(3-isopropylbenzyl)amino]propyl}-N3,N3-dipropyl-5-(1,3-thiazol-2-yl)isophthalamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

3-[(Dipropylamino)carbonyl]-5-(1,3-thiazol-2-yl)benzoic acid is dissolved in DMF (8 mL), and diisopropylethylamine (456 μL, 2.6 mmol), HATU (342 mg, 0.9 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-isopropylbenzyl)amino]butan-2-ol dihydrochloride (350 mg, 0.83 mmol) are added. The reaction stirred at room temperature 1 h. The reaction is partitioned between ethyl acetate and water. The organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/chloroform) provides the title compound as the free base. The residue is dissolved in diethyl ether (5 mL) and 1N hydrochloric acid in diethyl ether (2 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 663.3 [M+H]+.

Aufarbeitung

  1. customThe reaction is partitioned between ethyl acetate and water
  2. washThe organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 8% methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-00cfdeec197b4fe48f94306069b4e6dd
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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