N,N-Dichlorourethan → ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamate

HRID 1290619

Reaktionsgleichung

Reaktionsgleichung von HRID 1290619
[C:1]([C:5]1[O:6][C:7]2[C:13]([NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[C:12]([F:20])[CH:11]=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:21]N(Cl)C(OCC)=O>>[C:1]([C:5]1[O:6][C:7]2[C:13]([NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[C:12]([F:20])[CH:11]=[C:10]([Cl:21])[C:8]=2[N:9]=1)([CH3:2])([CH3:4])[CH3:3]

Komponenten

3

Edukt 2

HCID 26195N,N-DichlorourethanHCID 18916412ethyl N-(2-t-butyl-6-fluorobenzoxazol-7-yl)carbamate

Produkt 1

HCID 18916422ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamate

Versuchsvorschrift

The second starting material used to prepared those compounds in which the benzoxazole ring is formed first is a substituted-3-chloroaniline (STM2). The aniline (STM2) is reacted with the appropriate alkyl anhydride, for example trimethylacetic anhydride, under acidic conditions, yielding the corresponding N-(substituted-3-chlorophenyl)alkylamide (B-1). The aniline (STM2) can also be reacted with the appropriate propanoic acid (A-2), for example 2-methoxy-2-methylpropanoic acid, under basic conditions to form the appropriate N-(substituted-3-chlorophenyl)-substituted-alkylpropion-amide (B-2), for example N-(3-chloro-4-fluorophenyl)-2-methoxy-2-methyl-propionamide. The amides (B-1 or B-2) are in turn treated with n-butyl-lithium and cyclized with solid carbon dioxide, affording the corresponding [2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]carboxylic acid (C), for example, (2-t-butyl-6-fluorobenzoxazol-7-yl)carboxylic acid. The so-prepared carboxylic acid (C) is then reacted with ethyl chloroformate, 4-methylmorpholine, and sodium azide, yielding the corresponding [2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]carbonyl azide (C-1), which is treated with ethanol to form the corresponding ethyl N-[2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]carbamate (D). Additional substituents may optionally be added to the benzoxazole ring at this point. For example, ethyl N-(2-t-butyl-6-fluorobenzoxazol-7-yl)carbamate (D) is treated with N,N-dichlorourethane under acidic conditions, affording ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamate (E). The carbamates D and E are then reacted with ethyl 3-amino-4,4,4-trifluorocrotonate, sodium methoxide, and DBU to form the corresponding 3-[2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]-6-trifluoromethyl-2,4-(1H,3H)-pyrimidine-dione (F). The pyrimidinedione (F) is further reacted under basic conditions with an alkyl halide, for example methyl iodide, or O-(2,4-dinitrophenyl)hydroxylamine, or 1-aminooxysulfonyl-2,4,6-trimethylbenzene, affording the targeted 3-[2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]-1-alkyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (I) or 3-[2-alkyl- or 2-(substituted-alkyl)-substituted-benzoxazol-7-yl]-1-amino-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (II). Examples 1, 2, 4, and 5 provide the detailed procedures for this route.

Aufarbeitung

  1. additionAdditional substituents may optionally be added to the benzoxazole ring at this point

Quellen und Nachweise

ORD-Eintrag
ord-6cff3d64bb404499b371a16a442a7253
Quelldatensatz
uspto-grants-1998_05
Patentnummer
US05753595

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