Diisopropylethylamine → N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]-N3,N3-dipropylisophthalamide

HRID 14075

Reaktionsgleichung

Reaktionsgleichung von HRID 14075
[CH2:1]([N:4]([CH2:25][CH2:26][CH3:27])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[N:17]([CH2:21][O:22][CH2:23][CH3:24])[CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[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>[F:83][C:81]1[CH:82]=[C:77]([CH:78]=[C:79]([F:84])[CH:80]=1)[CH2:76][C@H:62]([NH:61][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([C:16]2[N:17]([CH2:21][O:22][CH2:23][CH3:24])[CH:18]=[CH:19][N:20]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:25][CH2:26][CH3:27])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=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

Komponenten

6

Edukt 4

HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210857843-((dipropylamino)carbonyl]-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]benzoic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Produkt 1

HCID 58802327N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]-N3,N3-dipropylisophthalamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred solution of 3-[(dipropylamino)carbonyl]-5-[1-(ethoxymethyl)-1H-imidazol-2-yl]benzoic acid (177 mg, 0.47 mmol), diisopropylethylamine (651 mg, 0.5 mmol), and HBTU (209 mg, 0.55 mmol) in methylene chloride (5 mL) is added a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (196 mg, 0.48 mmol) and diisopropylethylamine (130 mg, 1.0 mmol) in methylene chloride (5 mL). The reaction mixture is stirred at room temperature for 15 h and concentrated under reduced pressure. The residue is diluted with ethyl acetate (20 mL), washed with saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride) provides the title compound. APCI MS m/z 690.3 [M+H]+.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue is diluted with ethyl acetate (20 mL)
  3. washwashed with saturated sodium bicarbonate, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-f932d222e638411d918f844e3600083a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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