Diisopropylethylamine → [(2R,3S)-3-[3-acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoylamino]-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl ester

HRID 1454202Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1454202
[C:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][S:14]2(=[O:20])=[O:19])[CH:12]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:54][O:55][C:56]1[CH:57]=[C:58]([CH:82]=[CH:83][CH:84]=1)[CH2:59][N:60]([CH2:68][C@@H:69]([OH:81])[C@@H:70]([NH2:80])[CH2:71][C:72]1[CH:77]=[C:76]([F:78])[CH:75]=[C:74]([F:79])[CH:73]=1)[C:61](=[O:67])[O:62][C:63]([CH3:66])([CH3:65])[CH3:64]>CN(C=O)C.C(OCC)(=O)C>[C:63]([O:62][C:61](=[O:67])[N:60]([CH2:68][C@@H:69]([OH:81])[C@@H:70]([NH:80][C:7](=[O:9])[C:6]1[CH:10]=[C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][S:14]2(=[O:20])=[O:19])[CH:12]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)[CH2:71][C:72]1[CH:77]=[C:76]([F:78])[CH:75]=[C:74]([F:79])[CH:73]=1)[CH2:59][C:58]1[CH:82]=[CH:83][CH:84]=[C:56]([O:55][CH3:54])[CH:57]=1)([CH3:66])([CH3:64])[CH3:65]

Komponenten

7

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 575293073-Acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acidHCID 68827600tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)-carbamate

Produkt 1

HCID 57529282[(2R,3S)-3-[3-acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoylamino]-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxy-benzyl)-carbamic acid tert-butyl esterAusbeute 99,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 3-acetyl-5-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-benzoic acid (68.1 mg, 0.23 mmol), HATU (104.6 mg, 0.275 mmol) and Hunig's base (118.5 mg, 0.16 mL, 0.917 mmol) in DMF (1.1 mL) was stirred for 10 min and then tert-butyl 3-methoxybenzyl((2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate (100 mg, 0.23 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate, washed with H2O 3 times and concentrated under vacuum to give the title compound (164 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.48 (9H, s), 1.93-2.00 (2H, m), 2.32-2.38 (2H, m), 2.64 (3H, s), 2.88 (1H, dd, J=10, 15 Hz), 3.08-3.15 (1H, m), 3.20-3.23 (1H, m), 3.27-3.39 (2H, m), 3.38 (1H, m), 3.74-3.82 (6H, m), 3.96-4.00 (1H, m), 4.20-4.29 (2H, m), 6.76 (1H, m), 6.91-6.92 (3H, m), 7.05-7.08 (2H, m), 7.35 (1H, m), 8.04 (1H, m), 8.07 (1H, m), 8.11 (1H, m). HPLC retention time: 2.112 min (method A). MS (ESI) (M+Na)+ 738.28.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. washwashed with H2O 3 times
  3. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-2c86f4892ee94565b8d8bfaf24a785fb
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07476764B2

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