5-Hydroxyindoleacetic Acid → N-(2-(3,5-difluorophenyl)-1-(5-(o-tolyl)thiazol-4-yl)ethyl)-2-(5-hydroxy-1H-indol-3-yl)acetamide

HRID 1506636

Reaktionsgleichung

Reaktionsgleichung von HRID 1506636
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][CH:30]=[C:29]2[CH2:35][C:36]([OH:38])=O.CCN(C(C)C)C(C)C.[F:48][C:49]1[CH:50]=[C:51]([CH2:56][CH:57]([C:59]2[N:60]=[CH:61][S:62][C:63]=2[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=2[CH3:70])[NH2:58])[CH:52]=[C:53]([F:55])[CH:54]=1>CN(C=O)C>[F:48][C:49]1[CH:50]=[C:51]([CH2:56][CH:57]([NH:58][C:36](=[O:38])[CH2:35][C:29]2[C:28]3[C:32](=[CH:33][CH:34]=[C:26]([OH:25])[CH:27]=3)[NH:31][CH:30]=2)[C:59]2[N:60]=[CH:61][S:62][C:63]=2[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=2[CH3:70])[CH:52]=[C:53]([F:55])[CH:54]=1

Komponenten

6

Edukt 4

HCID 18265-Hydroxyindoleacetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902803772-(3,5-Difluorophenyl)-1-(5-(o-tolyl)thiazol-4-yl)ethanamine

Produkt 1

HCID 90281463N-(2-(3,5-difluorophenyl)-1-(5-(o-tolyl)thiazol-4-yl)ethyl)-2-(5-hydroxy-1H-indol-3-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

HATU (40 mg, 0.105 mmol) was added to a solution of 2-(5-hydroxy-1H-indol-3-yl)acetic acid (19.2 mg, 0.1 mmol) and DIPEA (0.02 mL, 0.12 mmol) in DMF (0.3 mL). After 10 minutes, 13D (33.1 mg, 0.1 mmol) in 0.2 mL of DMF was added to the reaction. The reaction was stirred for 2 hours. LC/MS shows desired product. Purified reaction mixture on prep reverse phase HPLC using 20-80% B over 20 min. (A=0.1% TFA/H2O; B=0.1% TFA/Acetonitrile). Combined pure fractions as determined by LC/MS and lyophilized to provide the desired product. 1H NMR (400 MHz, DMSO) δ 10.46 (s, 1H), 9.18 (s, 1H), 8.31 (d, J=8.2 Hz, 1H), 7.35-7.15 (m, 2H), 7.05 (t, J=7.1 Hz, 2H), 6.94 (dd, J=10.2, 5.8 Hz, 2H), 6.75 (t, J=7.2 Hz, 2H), 6.59-6.35 (m, 3H), 3.38 (s, 2H), 3.01 (d, J=7.5 Hz, 2H), 1.81 (s, 3H). MS (m/z) 504 [M+H]+.

Quellen und Nachweise

ORD-Eintrag
ord-bcb53f6eb1a444eeb1d93a335032e621
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09220710B2

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