Acetyl chloride → tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate

HRID 2203465Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2203465
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][C:26]2[CH:31]=[C:30]([F:32])[C:29]([S:33](=[O:52])(=[O:51])[N:34]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][C:42]=3[O:49][CH3:50])[C:35]3[S:39][N:38]=[CH:37][N:36]=3)=[CH:28][C:27]=2[F:53])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][N:14]=[C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:12]=3[CH:24]=2)[CH:7]=1.C(N(CC)CC)C.[C:61](Cl)(=[O:63])[CH3:62]>CN(C)C1C=CN=CC=1.ClCCl.C(OCC)(=O)C>[C:61]([N:16]([C:13]1[C:12]2[CH:24]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][C:26]3[CH:31]=[C:30]([F:32])[C:29]([S:33](=[O:52])(=[O:51])[N:34]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][C:42]=4[O:49][CH3:50])[C:35]4[S:39][N:38]=[CH:37][N:36]=4)=[CH:28][C:27]=3[F:53])[CH:9]=[CH:10][C:11]=2[O:15][N:14]=1)[C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])(=[O:63])[CH3:62]

Komponenten

7

Edukt 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 71558770tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate

Produkt 1

HCID 90389189tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamateAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate (0.20 g, 0.25 mmol), triethylamine (105 μL, 0.75 mmol) and 4-(dimethylamino)pyridine (0.030 g, 0.25 mmol) in dichloromethane (20 mL) at 0° C. was treated with acetyl chloride (36 μL, 0.5 mmol). The resulting solution was stirred for 1 h. The reaction mixture was diluted with ethyl acetate (70 mL), washed with saturated ammonium chloride (2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC to afford tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate as a colourless solid in 35% yield (0.05 g): 1H NMR (300 MHz, CDCl3) δ 8.15 (s, 1H), 7.68-7.63 (, m, 1H), 7.63-7.58 (m, 1H), 7.56-7.54 (m, 1H), 7.50-7.45 (m, 2H), 7.42-7.38 (m, 1H), 7.15-7.10 (m, 1H), 7.03-6.99 (m, 1H), 6.33-6.25 (m, 2H),6.19-6.17 (m, 1H), 3.72 (s, 3H), 3.63 (s, 3H), 2.67 (s, 3H), 1.31 (s, 9H); MS (ES+) m/z 727.5 (M−100), 729.7 (M−100).

Aufarbeitung

  1. washwashed with saturated ammonium chloride (2×50 mL) and brine (50 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-86a8ae08d3bf43d7a383edaa10eeedc9
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365578B2

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