6-(5-(Methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinoline → (+/-)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

HRID 2075343Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2075343
[Si:1]([O:8][CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:13]=1)[CH2:10][NH2:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CS([C:30]1[S:34][C:33]([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH:41]=[N:40][CH:39]=[CH:38]3)=[N:32][N:31]=1)(=O)=O.CS(C1SC(C2C=C3C(=CC=2)C=NC=C3)=NN=1)=O>CC(N(C)C)=O>[Si:1]([O:8][CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21])[CH:13]=1)[CH2:10][NH:11][C:30]1[S:34][C:33]([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH:41]=[N:40][CH:39]=[CH:38]3)=[N:32][N:31]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 579918986-(5-(Methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinolineHCID 57991914(+/-)-2-(tert-Butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethanamineHCID 670894316-(5-(Methylsulfinyl)-1,3,4-thiadiazol-2-yl)isoquinoline

Produkt 1

HCID 67089325(+/-)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

(±)-2-(tert-Butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethanamine and 6-(5-(methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinoline and 6-(5-(methylsulfinyl)-1,3,4-thiadiazol-2-yl)isoquinoline (prepared as in Scheme 7) was heated at 80-100° C. for 3 hours in DMA (0.3 M) to provide (±)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine. This intermediate was dissolved in THF and TBAF (1M in THF, 1.24 mmol) was added. After 16 hours, the mixture was concentrated in vacuo and the residue purified by flash chromatography on silica (eluting with DCM/MeOH gradients) to provide (±)-3-(1-hydroxy-2-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)ethyl)phenol (20 mg, 8%). LCMS (M+H) 365 calc. for C19H17N4O2S 365.1. 1H NMR (300 MHz, DMSO-d6): δ ppm 9.33 (s, 1H+OH), 8.56 (d, J=5.8 Hz, 1H), 8.27 (m, 2H), 8.18 (m, 2H), 7.92 (d, J=5.8 Hz, 1H), 7.14 (t, J=7.6, 1H), 6.84 (m, 2H), 6.65 (m, 1H), 5.58 (d, J=4.0 Hz, OH), 4.80 (m, 1H), 3.60 (m, 1H). 1H missing, covered by water signal.

Quellen und Nachweise

ORD-Eintrag
ord-7782da3070134df0933637d4b9e1e081
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919504B2

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