Hydrochloric Acid → Ethyl 2-(5-(4-(6-fluorobenzo[d]thiazol-2-ylamino)phenyl)thiazole-2-carboxamido)-3-methylbutanoate

HRID 1024445

Reaktionsgleichung

[CH3:1][CH:2]([CH3:25])[CH:3]([NH:8][C:9]([C:11]1[S:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)=[CH:14][N:15]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].Cl[C:27]1[S:28][C:29]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:30]=2[N:31]=1.Cl.[CH3:38]CO>O1CCOCC1>[F:36][C:34]1[CH:33]=[CH:32][C:30]2[N:31]=[C:27]([NH:22][C:19]3[CH:20]=[CH:21][C:16]([C:13]4[S:12][C:11]([C:9]([NH:8][CH:3]([CH:2]([CH3:25])[CH3:1])[C:4]([O:6][CH2:7][CH3:38])=[O:5])=[O:10])=[N:15][CH:14]=4)=[CH:17][CH:18]=3)[S:28][C:29]=2[CH:35]=1

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

A solution of Methyl 2-(5-(4-aminophenyl)thiazole-2-carboxamido)-3-methylbutanoate (Intermediate 2, 150 mg) and 2-chloro-6-fluorobenzo[d]thiazole (101 mg) in EtOH (3 ml) was heated at 55-60° C. to get clear solution. 4M aqueous HCl in 1,4-Dioxane (0.11 ml) was added to it and the reaction mixture was refluxed at 80° C. for 20 hours. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc:Pet ether, 2:8). The solid was crystallized in EtOAc/pet ether to give the title compound. Yield: 120 mg (53%); 1HNMR (DMSO-d6, 300 MHz): δ 10.76 (s, 1H), 8.66 (d, 1H), 8.37 (s, 1H), 7.88 (d, 2H), 7.80 (d, 2H), 7.77 (d, 1H), 7.64 (dd, 1H), 7.2 (m, 1H), 4.29 (m, 1H), 4.16 (q, 2H), 2.27 (m, 1H), 1.22 (t, 3H), 0.95 (d, 6H); MS (ES+) m/z 499 (M+1).

Aufarbeitung

customto get clear solution
customThe solvent was removed under reduced pressure
customthe residue was purified by silica gel column chromatography (EtOAc:Pet ether, 2:8)
customThe solid was crystallized in EtOAc/pet ether

Quellen und Nachweise

ORD-Eintrag: ord-de4712a4dcef449d9f2eac5838a3344d
Quelldatensatz: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08722901B2

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