4-Methylbenzyl chloride → 5-[3-(3-Chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amide

HRID 1266355Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1266355
C1(O[C:8](=[O:19])[NH:9][C:10]2[S:14][N:13]=[C:12]([SH:15])[C:11]=2[C:16](=[O:18])[NH2:17])C=CC=CC=1.[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C.[Cl:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[F:47])[CH2:42][NH2:43]>CN(C=O)C.Cl.O1CCCC1>[Cl:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[F:47])[CH2:42][NH:43][C:8](=[O:19])[NH:9][C:10]1[S:14][N:13]=[C:12]([S:15][CH2:20][C:21]2[CH:28]=[CH:27][C:24]([CH3:25])=[CH:23][CH:22]=2)[C:11]=1[C:16]([NH2:17])=[O:18]

Komponenten

8

Edukt 4

HCID 77224-Methylbenzyl chlorideHCID 81531DiisopropylethylamineHCID 1445393-Chloro-4-fluorobenzylamineHCID 178513777HCID 178513777, Verbindung

Produkt 1

HCID 538038185-[3-(3-Chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amideAusbeute 22,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of (4-carbamoyl-3-mercapto-isothiazol-5-yl)-carbamic acid phenyl ester (0.075 g, 0.25 mmol) in 0.5 mL of DMF was added 4-methylbenzylchloride (0.036 g, 0.25 mmol), followed by N,N-diisopropylethylamine (0.033 g, 0.25 mmol). After stirring for 18 hours at ambient temperature, tetrahydrofuran (1 mL) was added, followed by 3-chloro-4-fluorobenzylamine (0.081 g, 0.51 mmol). After stirring for 24 hours at 45° C., the mixture was diluted with 1M HCl, extracted 3× with ethyl acetate, and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by radial chromatography on silica gel eluting with ethyl acetate-hexane, affording 26 mg of 5-[3-(3-chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amide as a colorless solid. HPLC ret. time: 4.9 minutes. 1H NMR (400 MHz, acetone-d6) δ 7.95 (bs, 1H), 7.54 (dd, 1H, J=2, 7.2 Hz), 7.39 (m, 1H), 7.31-7.25 (m, 3H), 7.11 (d, 2H, J=8.0 Hz), 7.01 (bs, 2H), 4.48 (m, 4H), 2.28 (s, 3H) ppm; MS (APCl, m/z): 465 [M+H]+.

Aufarbeitung

  1. stirringAfter stirring for 24 hours at 45° C.
  2. extractionextracted 3× with ethyl acetate
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by radial chromatography on silica gel eluting with ethyl acetate-hexane

Quellen und Nachweise

ORD-Eintrag
ord-53c6905ba6b147e6a6e136bce629accc
Quelldatensatz
uspto-grants-2003_04
Patentnummer
US06548526B2

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