Pyrrole-l-carboxylic acids

A solution of 1 equivalent of isopropyl 5-p-methoxybenzoyl-l,2-dihydro-3H-pyrrolo[l,2-a]pyrrole-l-carboxylate in 10 ml of methanol is treated with a solution of 1 equivalent of potassium carbonate in 5 ml of water. The reaction mixture is refluxed under nitrogen atmosphere for 30 minutes, cooled, and evaporated to dryness. The residue is taken up in 10 ml of 10% aqueous hydrochloric acid and 50 ml of water and the resultant mixture extracted with ethyl acetate (2x50 ml). The combined extracts are dried over magnesium sulfate and evaporated to dryness under reduced pressure. Crystallization of the residue from ethyl acetate-hexane affords 5-p-methoxybenzoyl-l,2-dihydro-3H-pyrrolo[l, 2-a]pyrrole-l-carboxylic acid (anirolac) MP 187°-187.5°C. 

IH-Pyrrole-l-carboxylic acid, 2,5-dihydro-, 1,1-dimethylethyl ester)]... 

Ketorolac, ( )-5-Benzoyl-2,3-dihydro-IH-pyr-rolizirte-l-cttrboxylic acid 5 -benzoyl -1.2 -dihydro-3//-pyr. rolo[ 1,2-a]pyrrOle-l-carboxylic acid RS 37619. C jH,-... 

The synthesis of DPP-IV inhibitor Saxagliptin 5 also required (55)-5-amino-carbonyl-4,5-dihydro-lH-pyrrole-l-carboxylic acid, l-(l,l-dimethylethyl)ester 10 (Figure 16.3C). Direct chemical ammonolyses were hindered by the requirement for aggressive reaction conditions, which resulted in unacceptable levels of amide race-mization and side-product formation, while milder two-step hydrolysis-condensation protocols using coupling agents such as 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) [41] were compromised by reduced overall yields. To address this issue, a biocatalytic procedure was developed based on the Candida antartica lipase B (CALB)-mediated ammonolysis of (55)-4,5-dihydro-lH-pyrrole-l,5-dicarboxylic acid, l-(l,l-dimethylethyl)-5-ethyl ester 9 with ammonium carbamate to furnish 10 without racemization and with low levels of side-product formation. 

To a solution of 163 mg l-benzyl-2-benzoyl-4-methyl-5-oxo-6-methylene-l,2,3,5,6,6a-hexahydrocyclopenta[c]pyrrole-l-carboxylic acid methyl ester (0.403 mmol) in 2 mL 1,4-dioxane were added 42 fj,h Et3N (0.30 mmol), 184 ixL butyraldehyde (2.03 mmol), and 22 mg 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (0.080 mmol). The reaction vessel was sealed with a rubber septum and heated to 70°C for 6 h. The reaction mixture was then poured into 50 mL water, and the aqueous layer was extracted with Et20 (3 X 25 mL). The combined organic layers were washed with 20 mL brine, dried over MgS04, and concentrated under vacuum. After the addition of 5 mL hexanes to the residue, a white precipitate formed. The precipitate was collected by decantation and purified by flash chromatography (hexanes/EtOAc, 9 1 to 2 1, v/v) to afford 121 mg of the major diastereomer of 2-benzoyl-l-benzyl-4-methyl-5-oxo-6-(2-oxopentyl)-l,2,3,5,6,6a-hexahydrocyclopenta[c]pyrrole-l-carboxylic acid methyl ester (63% yield) and 19 mg of the minor diastereomer (10% yield). 

Pyrrole-2-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrole-3-carboxamide, N,N-dimethyl-conformation, 4, 194 Pyrrolecarboxamides synthesis, 4, 242 Pyrrole-2-carboxamides synthesis, 4, 148, 360 Pyrrolecarboxylhydrazides Curtius degradation, 4, 362 Pyrrole-2-carboxylic acid, l-benzyl-3-hydroxy-ethyl ester... 

Pyrrole-3-carboxylic acid, l-benzoyl-5-bromo-2,4-dimethyl-ethyl ester chlorination, 4, 271... 

S-[l[/ (R )],2a,3a(i,6ap]]-l-[2-[[l-(ethoxycarbonyl)-3-phenylpropyl]amino]-l-oxopropyl]octahydrocyclopenta[6]pyrrole-2-carboxylic acid... 

Intramolecular electrophilic reactions of substituted pyrrole-2-carboxylic acids or their amides lead to benzo[d]pyrrolo[l,2-a]azepinones. Acid 70 in this fashion undergoes Fiiedel-Crafts cyclization to furnish fused azepine 71 in good yield (Equation (6) (2000JOC2479)). 

The benzene ring has been proposed as an isosteric replacement in a dipeptide to enforce either the tram l1 1 or the cis conformation 312>31 (Scheme 1). Similarly, 2-(amino-methyl)pyrrole-l-acetic acid (8, R = H) has been proposed as a cis peptide bond mimic,141 having the same number of atoms between the amino and carboxylic acid functions as in a dipeptide. Several other amino- and carboxy-substituted aromatic structures have been used as spacers in peptides 2-, 3-, and 4-aminobenzoic acids (Abz, e.g., 7), 2-, 3-, and 4-(amino-methyl)benzoic acids (Amb, e.g., 2), 2-, 3-, and 4-(aminophenyl)acetic acids (APha, e.g., 5), 2- (4), 3-, and 4-(aminomethylphenyl)acetic acid (Ampa), (aminomethyl)pyrrole-, -thiophene-, and -furancarboxylic acids 6, (aminomethyl)pyrrole- 8 and -thienylacetic acids, and aminobiphenylcarboxylic acids. 

H-Pyrrole-3-carboxylic acid, l,2-dimethyl-4-formyl-, ethyl ester... 

In the light of these studies, it has been proposed that both proline and ornithine can be converted to pyrrole-2-carboxylic acid prior to halogenation subequently amide formation by reaction with 3-amino-l-(2-aminoimidazolyl)-prop-l-ene, derived from histidine, generates oroidin, followed by cyclization to stevensine (Scheme 10.3). 

A comparison of the absorption and fluorescence properties of 3,5-diaryl-l//-pyrrole-2-carboxylic acid ethyl esters reveals marked effects of/i-dimethylamino and o-methyl substituents on the phenyl group at C-3 and suggests that in the presence of these substituents emission occurs either from a charge transfer state or from a combination of charge transfer and locally excited states <2005NJC1258>. 

The Birch reduction has been applied to electron-deficient pyrroles substituted with a chiral auxiliary at the C(2)-position <1999TL435>. Using either (—)-8-phenylmenthol or (- -)-/ra /-2-(ot-cumyl)cyclohexanol as auxiliaries, high levels of stereoselectivity were obtained. Pyrrole 911, prepared from the l/7-pyrrole-2-carboxylic acid 910 in 90% yield, was reduced under modified Birch conditions (Scheme 176). The best conditions involved lithium metal (3 equiv), liquid ammonia and THE at —78°C. The addition of A, A -bis(2-methoxyethyl)amine (10 equiv) helped to reduce side reactions caused by the lithium amide formed in the reaction <1998TL3075>. After 15 min, the Birch reductions were quenched with a range of electrophiles and in each case 3,4-dehydroproline derivatives 912 were formed in excellent yields and with good diastereoselectivities. 

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