1 - -3 ethylcarbodiimide hydrochloride

Dime thy laminopropy I )-3-ethylcarbodiimide hydrochloride [l-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydrochloride] see entry on p. 212 in Chapter 4. 

Introduction of the C-6 acyl side chain proceeded with only modest selectivity in the presence of l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-DMAP, giving a 3 2 mixture of C-6 and C-7 acylated products (Scheme 26).60 However,... 

The only example to date of direct addition of a carbohydrate residue to a peptide chain was the coupling72 of 2-acetamido-4-0-(2-acetamido-2-deoxy-/ -D-glucopyranosyl)-2-deoxy-/ -D-glucopyranosylamine (37) with sodium poly(L-aspartate) in the presence of 3-(3-dimethylamino-propyl)-l-ethylcarbodiimide hydrochloride.73 The proportion of sugar residues introduced into the peptide chain was limited. 

Scheme 166 shows application of this methodology for preparation of hydrazide 1007. Thus, the reaction of acid 1004 with 1-hydroxybenzotriazole and EDC [l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride] gives ester 1005 that can be separated and characterized, but it rearranges slowly to isomeric form 1006 in solutions. However, both derivatives, 1005 and 1006, are found to be equally reactive toward hydrazine and afford hydrazide 1007 in 98% isolated yield <2002JOC9471>. 

Thioamides have been transformed into the corresponding nitriles. Treatment of primary thioamides by tellurium tetrachloride or selenium tetrachloride in combination with triethylamine affords nitriles.66 Treatment of primary amides and thioamides with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) gives nitriles.67 Reactions of thioamides with metal carboxylates in organic solvents enables the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material (Scheme 33).68... 

The aldehyde 38 was obtained from 35, by way of 36 and 37, by the carbodiimide—dimethyl sulfoxide oxidation procedure52 in the presence of 3-(3-dimethylaminopropyl)-l-ethylcarbodiimide hydrochloride (EDAC)53 and dichloroacetic acid. It was isolated in the form of its crystalline 1,3-diphenylimidazolidine derivative (39) by trapping the freshly prepared aldehyde 38 with N,N -diphen-ylethylenediamine. (This reagent was developed by Wanzlick and Lochel54 for the selective derivatization of aldehydes, and has been exploited for the isolation of nucleoside 5 -aldehydes55 and other aldehydo derivatives of carbohydrates by Moffatt and coworkers.52(b))... 

Figure 4.3 Enzymatic chiral synthesis of fluoroleucine derivative (EDC — 1 -(3-dimethylami-nopropyl)-3-ethylcarbodiimide hydrochloride)...

Benzyloxy-4-isopropyl(or 4-terf-butyl)-4-methyl-5(4//)-oxazolones 780 have been prepared from an A-benzyloxycarbonylamino acid 779 using l-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC HCl) as the cyclization agent (Scheme 7.237). Treatment of 780 with tetramethylfiuoroformamidinium hexafiuorophosphate (TFFH) has shown that they are possible intermediates in the fluorination of a-methyl-a-alkyl amino acids by TFFH. 

A flask was charged with the step 2 product, the step 3 product, and /V-(3-dimcthyl-aminopropyl)-A -ethylcarbodiimide hydrochloride and then treated with boron tribromide dissolved in CH2CI2 to remove the phenol protecting group. 

N -(3-Dimethylaminopropyl )-iV-ethylcarbodiimide hydrochloride dimethylaminopropyl) carbodiiomide hydrochloride (below). 

The following procedure describes the preparation and analysis of the (R)-a-methylbenzylamide of (R)-a-methylbenzenepropanoic add. A flame-dried, 10-mL, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar and a rubber septum is charged with 25 mg (0.15 mmol) of (R)-a-methylbenzenepropanoic acid, 31 mg (0.23 mmol) of 1-hydroxybenzotriazole hydrate, 44 mg (0.23 mmol) of 1-(3-dimethylamino)propyl-3-ethylcarbodiimide hydrochloride, and 0.50 mL of anhydrous N,N-dimethylformamide. This mixture is stirred at 23°C for 10 min, then cooled to 0°C in an ice-water bath. To the cooled solution, 24 pL (0.19 mmol) of R-(+)-a-methylbenzylamine and 86 pL (0.62 mmol) of triethylamine are added. Within 1 min, a fine white precipitate appears. The mixture is stirred for 1 hr at 0°C, then warmed to 23°C. After stirring for 20 hr at 23°C, the mixture is transferred to a 30-mL separatory funnel with 10 mL of dichloromethane. The product solution is extracted, sequentially, with four 10-mL portions of 1 N aqueous hydrochloric acid solution, 10 mL of saturated... 

Dimethylamino)propyl-3-ethylcarbodiimide hydrochloride Carbodiimide, [3-(dimethylamino)propyl]ethyl-, monohydrochloride (8) 1,3-Propanediamine, N -(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride (9) (25952-53-8) N.N-Dimethylformamide cancer suspect agent Formamide, N,N-dimethyl- (8,9) (68-12-2)... 

A,- 3-(Diiiietliylaiiiiiio)propyll-Ar-ethylcarbodiimide Hydrochloride/ 7-Aza-l,2,3-benzotriazol-l-ol Activation... 

The reaction of methyl 10, l l -dihydropyrrolo[ l, Z-b [ l, 2,5]bcnzothiadiazcpinc-l l -acetate 5,5-dioxide 73 or the corresponding ethyl ester 74 with potassium hydroxide in EtOH at 25 °C gave the acid 75 (Scheme 14), which upon treatment with trifluoroacetic anhydride in tetrahydrofuran (THF) underwent intramolecular cyclization to afford 76. The 1,2,5-thiadiazepines 73 and 74 were then heated with an excess of concentrated ammonium hydroxide to give the carboxamide 77. The acid 75 upon reaction with 4-chlorophenol, 4-chlorobenzyl alcohol, or 4-chloroaniline in the presence of iV-(3-dimethylaminopropyl)-iV -ethylcarbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) afforded the respective esters and amide 78-80 <1996FES425>. 

Ethylation of 352 followed by reduction with iron and subsequent hydrolysis afforded the amino acid 355, which underwent intramolecular cyclization catalyzed by iV-(3-dimethylaminopropyl)-./V -ethylcarbodiimide hydrochloride-iV,./V-dimethylaminopyridine complex to give 1,2,5-thiadiazepine 356 (Scheme 73). Similar methodology was employed to obtain the thiadiazepine 357 using (CH3)2C=CCHCH2Br for alkylation <2002JHC81>. 

Abbreviations BAL, backbone amide linker BSA, bis(trimethylsilyl)acetamide DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene DCE, dichloroethane DCM, dichloromethane DIC, 2-diisopropylcarbodiimide DIEA, diisopropylethyl amine DMAP, A,A-dimethylaminopyr-idine DMF, dimethylformamide DMSO, dimethyl sulfoxide EDC, l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide hydrochloride HBTU, [0-(7-azabenzotriazol-l-yl)-l, 1,3,3-tetramethyluronium hexafluorophosphate MCPBA, m-chloroperoxybenzoic acid NMP, N-methylpyrrolidinone NMM, A-methylmorpholine PfP, pentafluorophenol RT, room temperature TFA, trifluoroacetic acid THF, tetrahydrofuran. 

To the (2S)-2-benzyl-3-(l-methylpiperatin-4-ylsulfonyl)propionic acid (1.0 g, 3.064 mmol), the H-L-(4-thiazolyl)Ala amide of (2S,3R,4S)-2-amino-l-cyclohexyl-3,4-dihydroxy-6-methylheptane (1.11 g, 2.792 mmol), and 1-hydroxybenzotriazole (1.022 g, 7.563 mmol) in dimethylformamide (20 ml) was added N-methylmorpholine (0.35 ml, 3.2 mmol). The mixture was cooled to -23°C and treated with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.760 g, 3.96 mmol). After 2 h at -23°C and 14 h at room temperature, the reaction was poured into saturated NaHC03 solution (100 ml) and extracted into ethyl acetate (2x50 ml) which was washed with water (2x50 ml) and brine (50 ml) and then was dried over Na2S04 and evaporated to afford 1.94 g. Recrystallization from ethanol (15 ml)/hexane (90 ml) afforded 1.55g (79%) of (2S)-2-benzyl-3-(l-methylpiperazin-4-ylsulfonyl)propionyl-(L)-(4-thiazolyl)Ala-amide of (2S,3R,4S)-2-amino-l-cyclohexyl-3,4-dihydroxy-6-methylheptane as a white solid, melting point 169°-170°C. 

Separation of enantiomers of etodolac using two different derivitization agents and three chiral stationary phases has been studied [24]. Etodolac was converted to its anilide derivative with either 1,3-dicyclohexyl-carbodiimide or l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. Etodolac, derivatizing agent, aniline, and dichloromethane were allowed to incubate for 30 minutes, which was followed by addition of 1 M HC1. The organic layer was removed, washed, dried, and then injected into normal phase or reverse phase HPLC. The HPLC system consisted of a 250 x 4.6 mm (5 pm particle size) column packed with chiral stationary phases, and detection was effected by the UV absorbances at 254 and 280 nm. Separation of etodolac enantiomers was achieved on only one of the stationary phases when using 20% 2-propanol in hexane as the mobile phase at a flow rate of 2.0 mL/min. 

Fig. 8. Nicolaou s total synthesis ketalization and homologation of the carboxylic acid side chain. TFA = trifluoroacetic acid, EDC = l-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride, DMAP = 4-(/V,/ /-dimethylamino)pyridine.

Pathway C seemed to be especially attractive, because it should enable addition of acyl anion equivalents to a large number of readily accessible activated carboxylic acids (Figure 3.6.10). Thus diversity in all relevant positions should be readily attainable. High-loaded triphenyl phosphine resin 12 (1.6 mmol g-1) was alkylated with bromoacetonitrile under the action of microwave irradiation yielding phos-phonium salt 13 quantitatively. 13 was converted into stable ylide 14 by treatment with tertiary amine. Carboxylic acids were activated in the presence of N-(3-dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride (EDC) and reacted with 14 yielding acyl cyanophosphoranes 15. The reaction was monitored by ATR-IR coupling yields could be determined by spectrophotometric Fmoc-determination and were 90% for Fmoc-phenylalanine as reference amino acid. 

---