Bromo benzamide

V-bromo-benzamide is a useful method for the synthesis of the side chain of paclitaxel (taxol) from isopropyl cinnamate.219... 

This method has afforded some 2-phenyl-4-(/3-aminoethyl)-, and 2-pheny 1-4- (/3-disubstituted-aminoethyl) oxazoles from benzamide and the appropriate substituted bromobutanones.90 A 5-oxazolylethanol derivative is obtained from the corresponding substituted a-chloro ketone and amide in the presence of calcium carbonate (to neutralize the generated hydrogen chloride.)91 Condensation of a-bromophenylacetaldehyde and p-bromo-benzamide at 110°-120° gives 50% yield of 2-p-bromophenyl-5-phenyl-oxazole.18... 

A simple two-step synthesis of 5H-alkyl-2-phenyloxazol-4-ones has been reported by Trost and coworkers (Scheme 6.209) [377]. a-Bromo acid halides were condensed with benzamide in the presence of pyridine base at 60 °C to form the corresponding imides. Microwave irradiation of the imide intermediates in N,N-dimethylacetamide (DMA) containing sodium fluoride at 180 °C for 10 min provided the desired 5H-alkyl-2-phenyloxazol-4-ones (oxalactims) in yields of 44—82%. This class of heterocycles served as excellent precursors for the asymmetric synthesis of a-hydroxycar-boxylic acid derivatives [377]. 

Mannschreck et al. (44) examined the effect of substituents on the barriers to rotation in 2,4,6-trisubstituted benzamides. In /V-benzyl-A(-methyl-2,4,6-tri-bromobenzamide, the rotational barrier (AG ) is 23.8 kcal/mol at 35.8 to 40.6°C for the Z -> E process in quinoline (44). This should be compared with AG of 23.4 kcal/mol for the same process with the trimethyl compound (5). It is seen that steric effects are of primary importance, inasmuch as the van der Waals radii of the methyl and bromo groups are almost the same. 

A very interesting reported application of a resin combination (specifically for the synthesis of a wide variety of amides)12,63 is depicted by the synthesis of (V-benzyl-2-bromo-A-methy-benzamide (35), shown in Fig. 14, from simple starting materials. At first, benzylmethylamine is reacted with... 

N-Benzyl-2-bromo-N-methyl-benzamide (29). A solution of benzyl-N-methylamine (0.4 mmol), triethylamine (3 mmol), and 2-bromoben-zoylchloride (0.6 mmol) in DCM (1 ml) was shaken for 4 h. Amine-based resin (9) (100 mg) was added and the reaction mixture was shaken overnight. Upon filtration and concentration, the residue was partitioned between aqueous NaOH and EtOAc. Concentration of the organic layer afforded the purified product. MS 304, 306 (M + 1). 

N-Benzyl-2-bromo-N-methyl-benzamide (35). A suspension of morpholine resin (3, 0.63 mmol) in DCM (2 ml) was treated with. V-methyl-benzylamine (0.23 mmol) and 2-bromobenzoyl chloride (0.146 mmol). The reaction mixture was shaken for 5 h. Isocyanate resin (15, 0.2 g) was added followed by DCM (1 ml). The reaction mixture was then shaken for 16 h. Filtration of the resin followed by concentration of the filtrate gave the purified product. 

Bis(bis(hydroxymethyl)phosphino)ethane High-performance liquid chromatography AT-(2-Aminoethyl)-2-(diphenylphosphanyl)benzamide Ar,AT-Bis[2-(diphenylphosphino)phenyl]propane- 1,3-diamine AT-(2-Bromo)-2-(diphenylphosphanyl)benzamide 2-(Diphenylphosphanyl)-M-(2-hydroxyethyl)benzamide... 

A general two-step method has been developed for the synthesis of 5//-5-alkyl-2-phenyloxazoM-ones 251. This procedure involves the initial condensation of a-bromo acid halides 249 with benzamide to form an imide intermediate 250 followed by microwave-mediated cyclization in the presence of NaF to give the corresponding 4(5//)-oxazolones 251 (Scheme 73) <2004JA1944>. 

An example is as follows. After protection as a silyl ether, amidation of benzyl A-(5,6-0-isopropylidene-4-hydroxycyclohex-2-enyl)carbamate 229 (prepared from 3-bromo-lS,2S-0-isopropylidenecyclohexa-3,5-diene) with (6-bromo-3,4-methylenedioxy)benzoyl chloride gave the protected N-benzyloxycarbonyl-A-(cyclohex-2-enyl)benzamide 230. A modified Heck reaction of 230 in anisole produced the protected lycoricidine 231 in 27% yield (two steps) by A-detosylation. Acid treatment of 231 provided (-H)-lycoricidine (204) in 85% yield (Scheme 22). 

Fig. 13. Chemical structures for allosteric and ATP-competitive Eg5 inhibitors, (a) Monastrol ((S)-ethyl 1,2,3,4-tetrahydro-4-(3-hydroxyphenyl)-6-methyl-2-thioxopyrimidine-5-carboxylate), the first compound discovered which bound to the allosteric pocket the compound has an IC50 of 22 uM. (b) CK-f 06023 (N-((R)-f-(3-benzyl-7-chloro-3,4-dihydro-4-oxoquinazolin-2-yl)propyl)-4-bromo-N-(3-(dimethylamino)propyl) benzamide), which binds to the same allosteric pocket as Monastrol and has a Ki of f 2 nM. (c) CK-238273 N-(3-aminopropyl)-N-((R)-f -(3-benzyl-7-chloro-3,4-dihydro-4-oxoquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide), an optimized analog of CK-f 06023 which is in phase II and has a Ki of f. 7 nM. (d) 4-(2-(f -phenylethyl)thiazol-4-yl)pyridine, an ATP-competitive thiazole compound which was an initial hit from the Merck compound collection the compound has an IC50 of f f uM. (e) 4-(2-(f -(4-chlorophenyl)cyclo-propyl)thiazol-4-yl)pyridine, an optimized ATP-competitive thiazole compound with an IC50 of 290 nM.

In a separate development, Begley and Grimshaw [77JCS(P1)2324] attempted to cyclize the tertiary amide 142 by both photochemical and electrochemical methods. Reaction of 6,7-methylenedioxynaphthylamine 126 with 2-bromo-4,5-dimethoxybenzoylchloride 127 afforded the benzamide 129, which was methylated to give the tertiary amide 142. Whereas electrochemical reaction was unsuccessful, photochemical cyclization to the N-... 

Bromo(trimethylsilyl)mefhyl]-N.N-diisopropylbeiizaiiiide (13) Typical Procedure l l JV,N-Diisopropyl-2-[(trimethylsilyl)methyl benzamide (12 1.14 g, 3.9 mmol) in CCI4 (200 ml) (CAUTION) was added to NBS (1.01 g, 5.0 mmol) and benzoyl peroxide (10 mg). The mixture was heated under reflux and irradiated by a UV sun lamp for 90 min. The mixture was cooled to rt and the succinimide removed by filtration through Celite. The filtrate was concentrated under reduced pressure to give a crude oil. The crude product was purified by chromatography (silica gel) to give the a-bromosilane 13 as a white solid after recrystallization (pentane) yield 1.14 g (79%) mp 89-90 °C. 

Synthesis from l,2-Dithiole 3-thiones. 5-Aryl-l,2-dithiole-3-thiones (118) react with a-chlorobenzylidenephenylhydrazine (119), with simultaneous dithiole-ring opening and formation of (A -l,3,4-thiadiazolin-2-ylidine)-thioacetophenones (120). The use of ethyl bromo(phenylhydrazono)-acetate similarly affords (5-ethoxycarbonyl-3-phenyl-A -l,3,4-thiadiazolin-2-ylidene)thioacetophenone, which is saponifiable to the corresponding 5-carboxylic acid. The reactions resemble Huisgen s synthesis of iV-(3,5-diphenyl-A -l, 3,4-thiadiazolin-2-ylidene)benzamide from (119). 

A -[3,5-Bis(trifluoromethyl)phenyl]-A -hydroxy-3,5-bis(trifluoromethyl) benzamide, B-00465 5-Bromo-A, 2-dihydroxybenzamide,... 

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