Trifluoroacetic acid → methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidate

HRID 1473453Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1473453
[C:1]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([N:26](CC3C=CC(OC)=CC=3OC)[C:27]3[S:28][CH:29]=[CH:30][N:31]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1)#[N:2].[C:43](O)(C(F)(F)F)=[O:44]>C(Cl)Cl>[S:28]1[CH:29]=[CH:30][N:31]=[C:27]1[NH:26][S:23]([C:19]1[CH:18]=[C:17]2[C:22](=[CH:21][CH:20]=1)[C:13]([C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:11])([F:12])[F:10])=[CH:8][C:3]=1[C:1](=[NH:2])[O:44][CH3:43])=[N:14][CH:15]=[CH:16]2)(=[O:25])=[O:24]

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 866874981-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Produkt 1

HCID 86687499methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidateAusbeute 88,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-(2-cyano-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.011 g, 0.018 mmol) was dissolved in 1 mL of DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated, dissolved in methanol, and passed through an SCX ion exchange column (pre-wetted with methanol). The column was flushed several times with methanol, then the product was liberated by flushing the column several times with 2.0 M ammonia in methanol. The product-containing filtrate was concentrated to afford an orange solid. The material was purified via silica gel column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM) to afford methyl 2-(6-(N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)-5-(trifluoromethyl)benzimidate (0.008 g, 0.016 mmol, 9.10% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.90 (br. s., 1H), 8.78 (br. s., 1H), 8.66 (d, J=5.6 Hz, 1H), 8.58 (s, 1H), 8.14 (d, J=5.0 Hz, 1H), 8.06 (br. s., 1H), 7.99 (d, J=7.5 Hz, 1H), 7.89-7.83 (m, 1H), 7.77 (d, J=8.5 Hz, 2H), 7.28 (d, J=4.6 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.02 (s, 3H). m/z (ESI) 493.2 (M+H)+.

Aufarbeitung

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in methanol
  3. customThe column was flushed several times with methanol
  4. customby flushing the column several times with 2.0 M ammonia in methanol
  5. concentrationThe product-containing filtrate was concentrated
  6. customto afford an orange solid
  7. customThe material was purified via silica gel column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-7f03b8ae998c4314a911d6989f95ab66
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012443B2

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