Carboxamides 2-bromo

Nucleophilic attack by carbanion occurs in the reaction of 2-nitrobenzamides 154 treated with sodium ethoxide (72JCS(P1)835). The reaction mixtures usually contain small amounts of nitrile 155 and carboxamide 156, the product of decarboxylation 158 being usually the principal product (Scheme 24). The corresponding bromo derivatives under the used conditions did not react. 

Bromo atom of ethyl (3S)-10-bromo-3-methyl-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate was change for hetaryl groups with tributylstannyl derivatives of heterocycles in the presence of (Ph3P)2Pd(II)Cl2 in boiling toluene (OOMIPIO). 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylates, 6-carboxamides and their 1,1-dioxide derivatives were prepared from 7-chloro derivatives in the... 

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

HPA = (4-pyridylthio)aceticacid 2-fur = 2-furoate a-fur = a-furoate = ([Pg.116]

The bromodeoxyaldonolactones have been used for the preparation of aminodeoxy aldonic acids and aminodeoxy sugars via azido derivatives (45,46). Likewise, a- and /J-aminopolyhydroxy acids have been prepared by treatment of the bromodeoxyaldonolactones with liquid ammonia (47). Thus, 3-amino-3-deoxy-D-threonic acid and 3-amino-3-deoxy-D-arabin-onic acid (40b) were obtained from 2-bromo-2-deoxy-L-threono- or D-xy-lono-1,4-lactone (38). It was shown that 2,3-epoxy carboxamides (namely, 39) are intermediates of the reaction. Heating at 90° for long periods led to the 3-amino-3-deoxyaldonamides, which upon acid hydrolysis yielded the corresponding aldonic acids. 

Quantitative cyclization of Ai-chloro-Ai-methoxybiphenyl-2-carboxamide (22, X = Cl) to iV-methoxyphenanthridone (23) using AgBp4 in benzene was the first example of such chemistry (equation 6). The cyclization could also be effected thermally in refluxing benzene or catalysed by molecular iodine in the dark. The corresponding A-bromo- and A-iodoamides, formed in situ, reacted at room temperature. ... 

The Reformatsky reactions of ethyl a-bromopropionate and related esters with N-substituted 6-bromo-2-oxochromene-3-carboxamides in a mixed diethyl ether-benzene-HMPA-THF solvent system give substituted 9-bromo-2,3,4,4a,5,10b-hexahydro-l//-chromeno[3,4-f]pyridine-2,4,5-triones (HMPA = hexamethylphosphoramide Scheme 45) <2004RJ0892>. Without the THF present in the mixed-solvent system, the reaction stops at the intermediate Wbenzyl-6-bromo-4-(l-alkoxycarbonylalkyl)-2-oxochroman-3-carboxamide stage. 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

However, sulfonamides are much more difficult to hydrolyze back to the amine than are carboxamides. In peptide synthesis (Section 25-7C) the commonly used sulfonyl protecting groups are 4-methylbenzenesulfonyl or 4-bromo-benzenesulfonyl groups. These groups can be removed as necessary from the sulfonamide by reduction with sodium metal in liquid ammonia ... 

Triazolo-fused dioxazepine 201 was obtained as a by-product in Suzuki coupling reactions of 5-bromo-l-(2-hydroxyethoxymethyl)-l,2,4-triazole-3-carboxamide the reaction, however, can be shifted towards 201 by using a strong base <2007TL2389>. 

Notes (a) Loaded with the Yamaguchi method, (b) Fmoc-amino acid loaded with DIC/ DMAP, deprotected and reacted with bromo-acid. (c) Symmetric diamine loaded on the nitrophenyl carbonate derivative of Wang resin and subsequently reacted with bromo-acid. (d) Piperazine carboxamide scaffold reacted with the nitrophenyl carbonate derivative of Wang resin. 

N-(3-chloro-5-methoxycarbonylphenyl)-5-bromo-l,2,3,4-tetrahydro-quinoline-8-carboxamide was obtained from 8-bromo-6,7-dihydro-lH,3H,5H-pyrido[3,2,l-z/][3,l]benzoxazine-l,3-dione with methyl 3-amino-5-chlorobenzoate in NMP at 170 °C for 16 h (07WOP2007/028789). 

Reaction of 5-bromo-l,2,3,4-tetrahydroquinoline-8-carboxylic acid with COCl2 in THF at room temperature for 16 h gave 8-bromo-6,7-dihy-dro-lH,3H,5H-pyrido[3,2,l-//J[3,lJbenzoxazine-l,3-dione in 80% yield (07WOP2007/028789). 8-Bromo-2-aryl-2,3,6,7-tetrahydro-lH,5H-pyrido [3,2,1-zy]quinazoline-l,3-diones were also prepared in the reaction of N-aryl-5-bromo-l, 2,3,4-tetrahydroquinoline-8-carboxamides and ClC02Ph in boiling 1,2-dichloroethane for 30 min. 

The treatment of N-(2-hydroxyethyl),N-(4-fluorophenyl)-4-benzyloxy-3-methoxypyridine-2-carboxamides with a mixture of polystyryldiphe-nylphosphine, imidazole, and I2 in CH2C12 at ambient temperature overnight yielded 9-methoxy-2-(4-fluorophenyl)-3,4-dihydro-l H,8H-pyrido [l,2-fl]pyrazine-l, 8-diones (06WOP2006/066414). When N-(2-hydro-xyethyl),JV-(4-fluorophenyl)-4-benzyloxy-3-methoxy-6-bromopyridine-2-carboxamides was heated in HBr-AcOH solution (38%) at 100 °C for overnight 6-bromo-9-hydroxy-2-(4-fluorophenyl)-3,4-dihydro-lH,8H-pyrido [l,2- ]pyrazine-l,8-diones were the products. 

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