Ethyl mesylate

Ethyl mesylate, methanesulfonic acid ethyl ester, NSC-26805. 

In view of the unexpected effects of the C-2 and C-3 substituents on the reaction of C-4 sulfonates, it is worthwhile to point out the observations made with some 2,3-dideoxy derivatives. Treatment of ethyl 2,3-dideoxy-4,6-di-0-methylsulfonyl-D-ert/ hro-hexopyranoside (40) with sodium iodide and acetone at 115°C. caused the displacement of the C-6 mesylate group selectively to give 41. Catalytic hydrogenation then gave the corresponding ethyl 4-0-methylsulfonyl-2,3,6-trideoxy- -D-en/ /iro-hexoside in good overall yield (83%) (72). 

Ethyl 1/7-azepine-l-carboxylate (1) yields the [2 + 4] enc/o-cycloadducts 16 with isobenzofuran (15, R = H) and with 1,3-diphenylisobenzofuran (15. R = Ph).251 l-Mesyl-lZ/-azepine behaves likewise. 

Surprisingly, 2,5-dimethyl-3,4-diphenylcyclopentadienone (17) with ethyl l//-azepine-l-carb-oxylate (1) behaves as both diene and dienophile to give a separable mixture of the [4 + 2] 18 and [2 + 4] 19 7t-ewfo-cycloadducts,251 259 the latter being incorrectly formulated in the original paper251 as the opposite regioisomer. l-Mesyl-1//-azepine under similar conditions yields only the [2 + 4] cycloadduct [42% mp 158°C (dec.)],157 251 whereas with tetraphenylcyclopen-tadienone low yields of the [4 + 2] (9.7%) and [6 + 4] (1.7%) rc-adducts are reported.157... 

C7Hf,N202 5444-02-0) see Nevirapine (35,4a5,8JL5)-2-[(2/f)-2-[(4S)-4,5-dihydro-2-(3-hydroxy-2-methylphenyl)-4-oxazolyl)-2-hydroxyethyl]- -(l,l-di-methylethyl)decahydro-3-i oquinolinecarboxamidc (C2f,H3yN304 188936-07-4) see Nelfinavir mesylate 3-[(4S)-4,5-dihydro-4-[(li )-2-hydroxy-l-[(methylsulfo-nyl)oxy]ethyl]-2-oxazolyl]-2-methylphenol (CpHpNOf S) see Nelfinavir mesylate... 

C21H21N3O9 4199-35-3) see Minocycline (/ )-[2-(dimethylamino)-2-oxo-l-[(phenylthio)methyl] ethyl]carbamic acid phenylmethyl ester (C,9H22N20iS 197302-34-4) see Nelfinavir mesylate lV-[3-[3-(dimethylamino)-l-oxo-2-propenylJphenyl]acet-amide... 

O-Acylated or mesylated oximes such as the ethyl carbonate of acetophenone-oxime 1772 react with TIS 17, with Beckmann rearrangement to the imidoyl iodide 1773, which adds phenylmagnesium bromide in situ to give 61% of the sec-... 

The reaction of 5-[2-(iV,./V-dimethylamino)ethyl]-l,2,4-oxadiazole with methyl iodide forms the quaternary ammonium salt 170 (Scheme 22), which undergoes elimination in the presence of base (diisopropylethylamine (DIEA), TEA, l,8-diazabicyclo[4.3.0]undec-7-ene, etc.) to form an intermediate 5-vinyl-l,2,4-oxadiazole 171, which undergoes in situ Michael addition with nucleophiles to furnish the Michael adducts 172. As an example, also shown in Scheme 22, 3-hydroxy-pyrrolidine allows the synthesis of compound 172a in 97% yield. Mesylation followed by deprotonation of the 1,2,4-oxadiazole methylene at C-5 enables Sn2 displacement of the mesylate to give the 5-azabicycloheptyl derivative 173, which is a potent muscarinic agonist <1996JOC3228>. 

The cyclobutanone (255) reacted with acid to furnish the keto-acid (259). Upon esterification, ketalization and reduction, (259) was converted to the alcohol (260). Mesylation of the alcohol (260) and then treatment of the mesylate with NaN3 in DMSO provided the azide (261). The azide (261) was then transformed to the urethane (262) by reduction and ethyl chloroformate reaction. The urethane (262) was deketalized by acid, nitrosated by N204—NaOAc and decomposed by NaOEt—EtOH to give the ketone (263) 89). The ketone (263) served as a starting material for the synthesis of veatchine (264)90). 

N-NeoDentyl)-4-DihexylaminoDvrldinium Bromide (3h) The neopentyl salt was prepared in a similar manner from neopentyl mesylate, but reaction was carried out neat at 130 for 72 hr. Higher temperatures cannot be used, due to decomposition of neopentyl mesylate. The crude product was dissolved in water, basifled to neutralize any pyridinium salt, and was washed with petroleum ether to remove amine and unreacted neopentyl mesylate. The aqueous phase was acidified with HBr, and extracted with methylene chloride, to afford crude salt. Recrystallization from 20 1 ethyl acetate/acetonitrile affords the product (mp = 169-170 ). 

Figure 4.10 Selected ion-monitoring chromatograms of the thiocyanate and isothiocyanate derivatives of methyl, ethyl and isopropyl mesylates (final concentrations 0.25 pg/ml). Reproduced from [60] by permission of the Royal Society of Chemistry.

Pankova and Tichy prepared all four stereoisomeric 4-rerr-butyl-2-aminomethyl-l-cyclohexanols and cyclized them with ethyl benzimidate to hexahydro-l,3-benzoxazines 158-161 (74CCC1447). From the A-acyl O-mesylate derivatives 162 and 163 on thermal cyclization or thionyl chloride treatment, ring closure occurred with inversion and resulted in 158 and 159 (74CCC1447). 

Gemcitabine (Gemzar ) is prepared from the 2,2-difluoro-2-deoxyribose, itself available by the addition of the Reformatsky reagent of ethyl bromodifluoroace-tate on the (R)-2,3-0-isopropylidene glyceraldehyde. The condensation of the corresponding mesylate with di(trimethylsilyloxy)pyrimidine provides gemcitabine [93]. The control of the stereoselectivity of the Reformatsky reaction is difficult (Fig. 30) [95]. Other approaches involving the fluorination of D-pyranoses have been proposed (Fig. 31) [96]. 

The stereoselective intermolecular cycloaddition of azides to chiral cyclopenta-none enamines was reported, but both product yields and enantiomeric excesses (ee) were low (24) (Scheme 9.24). Ethyl azidoformate (115) and A-mesyl azido-formamimidate (116) underwent 1,3-dipolar cycloaddition with the monosubsti-tuted chiral enamine 114 to give products 117 and 118 in low yields with ee of 24 and 18%, respectively. Intermolecular cycloaddition of the A-mesyl azidoforma-mhnidate 116 with the disubstituted C2-symmetric chiral enamine 119 proceeded with good diastereoselectivity to give compound 120 in 18% yield. On cleavage of the enamine unit, compound 120 afforded 118 with low ee. 

Druker BJ. Cireumventing resistanee to kinase-inhibitor therapy. N EnglJMed 2006 354 2594-2596. Bradeen HA, Bide CA, O Hare T et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an A-ethyl-A-nitrosourea (ENU)-based mutagenesis sereen high effieaey of drug eombinations. Blood 2006 108 2332-2338. 

In a similar approach, Kasture and coworkers describe the use of neat substrate (ethyl acetate both as alcohol donor and as the reaction medium) in the preparation of chirally pure S-(-)-l,4-benzodioxan-2-carboxylate, an important drug intermediate used in the synthesis of doxazosin mesylate, from racemic l,4-benzodioxan-2-carboxylic acid [138]. Again, CaLB catalyzed the transesterification reaction with good enanhoselectivity (E = 160) and acceptable enantiomeric excess (>95%) and chemical yield (50%). 

The 12-step synthesis of imatinib mesylate (1) in the manufacturing process was accomplished by Novartis in an astonishingly short time. The synthesis began with a condensation reaction between 6 and ethyl formate. Deprotonation of the methyl group on 3-acetylpyndine (6) using freshly prepared sodium methoxide afforded an enolate. Condensation of the enolate with ethyl formate was followed by exchange with to produce 3-dimethylamino-l-(3-pyridyl)-2-propen-l-one (7). could be prepared from the condensation of 6 and N,N-... 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

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