Dimethylformamide dimethylacetal

The enamine 141 can be cyclized to the [l,2,4]triazolopyridopyrimidine 142 upon treatment with sodium ethoxide (Scheme 40) <2002M1297>. This fused tricyclic system may also be obtained, like the pteridine analogue (cf. Scheme 38), from the reaction of hydrazonoyl halides and pyridopyrimidines such as 143, and also by treatment of the triazolopyrimidine 144 with dimethylformamide dimethylacetal (DMF-DMA) dimethylacetal and subsequent ring closure <2003MOL333, 2003HAC491> (Scheme 41). Another series of triazolopyridopyrimidines, for example, 146, can be prepared from a hydrazine-substituted pyridopyrimidine 145, in two ways either directly by reaction with an acid chloride, or via a derived hydrazone (Scheme 42) <1996MI585>. 

Nagai et al. carried out various transformations with camphor-fused amino[l,2,4]triazine 191 <1998JHC293> (Scheme 39). Reaction of 191 with chlorocarbonylsulfenyl chloride yielded the fused thiadiazolone 192 in high yield (83%). The same starting compound also proved to be suitable for the synthesis of the fused triazole derivative 193. To this end, 191 was first subjected to two subsequent transformations first by dimethylformamide dimethylacetal followed by treatment with hydroxylamine hydrochloride to give an Ar-hydroxyamidine 193 in 90% overall yield, and then this compound was treated with polyphosphoric acid to yield the fused triazole product 194 in 92% yield. 

The condensation of 207 with dimethylformamide dimethylacetal affords dimethylaminomethylenefuranone 208 in high yield and... 

The synthesis of zaleplon (Scheme 15.3) starts by condensing acetophenone derivative 13 with dimethylformamide dimethylacetal (DMF-DMA) to provide enamine 14 (Mealy et ah, 1996 Dusza et al., 1987). A subsequent alkylation with ethyl iodide in the presence of sodium hydride gave 15. Zaleplon (2) is assembled by condensing amino-pyrazole 16 with enamine 15 in refluxing acetic acid. 

Several syntheses of indiplon have been described and two routes are shown in Scheme 15.5 (Sorbera et al., 2003 Dusza et al., 2002). Treatment of acetophenone 26 with refluxing dimethylformamide dimethylacetal (DMF-DMA) provided enamide 27. Alkylation of the amide with methyl iodide using NaH in DMF afforded 28. 3-Ketonitrile 29 was treated with DMF-DMA to give enamide 30. Cychzation with aminoguanidine produced aminopyrazole 31. The condensation of enamide 28 with aminopyrazole 31 in acetic acid furnished indiplon (4). Alternatively, enamine 28... 

An interesting N-methylation procedure for pyridazin-3(2//)-ones is based on a simple heating of the substrates with dimethylformamide dimethylacetal (DMFDMA) in DMF <2002SC1675>. 

Enamines and Formamidines. Enamines, prepared from methylpyridines, methyl-pyridazines, methylpyrimidines or methyltriazine, and A, A -dimethylformamide dimethylacetal or ferf-butoxybis(dimethylamino)methane, react with 2-phenyl-5(4//)-oxazolone 146 to afford the unsaturated 5(477)-oxazolones 199 and 201 that are intermediates in the synthesis of fused pyridones 200 and pyridotriazi-nones 202, respectively (Scheme 7.61). ... 

Bis(7-methylpurin-8-yl)methane underwent a high-yielding nitrosation and also reacted with dimethylformamide dimethylacetal under mild conditions at the exocyclic carbon, reflecting the high acidity of the hydrogens on the bridging carbon <1998JOC436> see Section 10.11.5.2.6. The introduction of 6-fluoromethyl and 6-difluoromethyl... 

A concise preparation of retinoids via new enaminodiesters synthons was described by Valla et al. [41]. For example, all -retinoic acid was synthesized within one day by a one-pot process. The enaminodiester synthon was prepared from methyl isopropylidenemalonate and dimethylformamide dimethylacetal (DMF-DMA) and then condensed with the lithium enolate of (3-ionone. A Grignard reaction with the obtained ketodiester led to the retro carbomethoxyretinoate. Saponification and concomitant decarboxylation, provided mainly all E retinoic acid (all E/ 3Z 90/10, 72% from P-ionone), Fig. (17). 

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

A solution of 153.0 g (1.26 mole) of 2-acetylpyridine (Aldrich) and 180.0 g (1.41 mole) of Af,N-dimethylformamide dimethylacetal (Aldrich, 94% pure) in 250 mL of toluene are heated to reflux in a 1-L, round-bottomed flask. Methanol is gradually removed by fractional distillation through a 20-cm... 

Vigreux column. When no more methanol distills over (ca. 24 h), the dark brown reaction mixture is reduced in volume by the distillation of 100 mL of toluene. While the flask is still hot, 300 mL of cyclohexane are added with vigorous stirring and a yellow, crystalline solid comes out of solution. At this point, the copious amount of solid makes stirring difficult. The mixture is allowed to stand overnight and the yellow solid is collected by suction filtration. The solid is washed with 2 1 cyclohexane/toluene (ca. 300 mL) and, then cyclohexane and is allowed to air dry. The solid is then dried in a vacuum dessicator (25°C, 24 h) to remove the last traces of N,N-dimethylformamide dimethylacetal (a small amount of sublimation of the product will occur). Failure to completely remove the last traces of N,JV-dimethylformamide dimethylacetal results in the gradual darkening of the product over several months time. Yield 190.3 g (86% based on 2-acetylpyridine), mp 127-128°C. 

Condensation of amine 277 with dimethylformamide dimethylacetal (DMF/DMA) gave A, A-dimethyl-./V -(5-methyl-l, 2,4-triazolo[l, 5-a]pyrim-idin-7-yl)formamidine (278), whose reaction with hydroxylamine gave the formamidoxime 279 (89EGP264438 90ZC320).The amine 280 and the hydrazine 282 can be transformed into the amidine 281 and amidrazone 283, respectively (90ZC320) (Scheme 54). 

Whereas free thiol or thione functions are readily alkylated, especially in basic media (62JCS3124), 2-alkylthiouracils normally alkylate preferentially at N-3 (82ACS(B)15). With dimethylformamide dimethylacetal, significant... 

Pd-catalyzed coupling reactions at the 5-position of 6-phenyl-3(2W)-pyridazinones using a retro-ene transformation have been reported <02SL2062>, and the Pd-catalyzed arylation of 4-bromo-6-chloro-3-phenylpyridazine has been shown to be efficient and regioselective <02SL223>. The N-methylation of substituted 3(2//)-pyridazinones with Ai,iV-dimethylformamide dimethylacetal has been explored <02SC1675>, as have the preparation of 3-nitro-, -nitroso- and -chloro-derivatives of... 

Acetophenone (30.6 g) and N,N-dimethylformamide dimethylacetal (100 g, 94% by weight) in acetonitrile were refluxed overnight, cooled, and concentrated. The solid was dissolved in 400 ml DMF, cyanoacetamide (19.4g) and sodium methoxide added, and the mixture heated 5 hours at 100 °C. It was cooled, diluted with water, acidified with HCl to a pH = 5, and the product isolated. H-NHR data supplied. 

Subsequent industrial processes for preparing tropenol using dimethylformamide, dimethylacetal, meteloidin (3), 2,2-diphenylpropionic acid, and scopine ester-metho-bromide (4) are described. 

Substituted pyrimido[4,5-c/Jpyrimidines are synthesized by reaction of 5-acyl-6-aminouracils with dimethylformamide dimethylacetal (DMF-DMA) and subsequent cyclization by ammonia. When nitromethane is used instead of ammonia, 6-nitropyrido[2,3-pyri-midines are obtained by direct cyclization of 5-acetyl-6-aminouracil using DMF-DMA and DMF-POCl3, respectively, under drastic conditions [91JMC(ip)] (Scheme 59). 

Methylation of 3-methylquinoxalin-2(l//)-one with dimethylformamide dimethylacetal (DMFDMA) affords l,3-dimethylquinoxalin-2(17/)-one. ... 

In the case of the enaminonitrile XVIIa, coupling through the phenyl ring is observed [127a]. Enamines related to the key intermediate in thiamine diphosphate-dependent enzymatic pathways lead to dimers in a one-electron oxidation via a thiazolium cation radical as intermediate [127b]. Anodic oxidation of enaminones, prepared from / -substituted acetophenones and A,A-dimethylformamide dimethylacetal, afford dimers and substituted furans in fair yield [127c]. 

The direct conversion of carboxyhc acids and amino alcohols to 4,5-dihydrooxazoles has been achieved in yields of up to 80% using triphenylphosphine, hexachloroethane and triethylamine <93T9353> and in yields up to 97% with boric acid <85JCS(P1)1865>. Amino alcohols react with dimethylformamide dimethylacetal in the presence of Amberlite resin to give the oxazoles in 65-90% yield <9UOCl961>. 

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