5-methyl-lH-tetrazole

The use of unprotected a,a -dihydroxyacetone (149a, R=H, Scheme 4.35) as source of nucleophile in the reaction with aromatic, heteroaromatic and aliphatic aldehydes was very interesting (Scheme 4.35). Threonine derivatives 144c catalyzed this reaction in DMF and 5-methyl-lH-tetrazole to give mainly the isomer syn-150 (66-94% de) with excellent results, after the acetylation process [233c]. Lowest yields were encountered for aliphatic aldehydes whereas the enantioselectivity was uniform independently of nature of aldehydes used. Also benzyl- or tcrt-butyldimethylsilyl-protected a,a -dihydroxyacetone (149, R=Bn or SiMe Bu ) could be used as source of nucleophile in this transformation. The reaction was carried out in NMP as solvent and in the presence of water at 25°C, affording the expected product in good results (65-94% yield, 60-75% de, 93-98% ee). 

The only successful catalyst for the reaction of unprotected DHA with aliphatic acceptors is 0-tBu-threonine-based amide 85, with 5-methyl-lH-tetrazole as a cocatalyst [107]. 

C24H24NSO5S 66510-99-4) see Latamoxef diphenylmethyl 7(/f)-amino-3-(l-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate (C23H22N6O3S2 53090-86-1) see Cefbuperazone diphenylmethyl 7-amino-3-[(Z)-f -propenyl]-3-cephem-4-carboxylate... 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH]-tetrazol-5-ylthio-methyl moiety at C-3 and an acylated p-hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21]. 

A-(l//-5-Tetrazolyl)-10-(2,3-dimethylpentanoylamino)-7-methyl-4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxamide was prepared on treatment of the 3-carboxylic acid with l,l -carbonyldiimidazole in dimethyl-formamide at ambient temperature under nitrogen, then with 5-amino-lH-tetrazole at 100°C for 1 h (85EUP143001). Treatment of lO-(acylamido)-... 

Amir.o-1-mcthyUa tetraiclc or 5 Amine-]-methyl-lH-tetrazole, called in Beil 1-Methyl-5-amino-tetrazol or l-Methyl-tetrazolon-( 5)-imid, H2N-C-N(CH,)-N... 

Moxalactam disodium is a drug entity which was discovered at Shionogi and Company, Limited, Osaka, Japan, and codeveloped with Eli Lilly and Company. The drug is marketed under the trade names of MOXAM and LAMOXAM . The chemical entity is the disodium salt of (6R,7R)-7-[[carboxy(4-hydroxy-phenyl)-acetyl]amino]-7-methoxy-3-[[l-methyl-lH-tetrazole-5-yl)thio]-methyl]-8-oxo-5-oxa-l-azabi cyclo[4.2.0]oct-2-ene-2-carboxyli c acid. 

The epioxazoline is successively treated with chlorine, sodium iodide, cuprous oxide and boron trifluoride to produce the exomethylene compound (V). Methoxylation using chlorine with a methoxide followed by reaction with 1-methyl-lH-tetrazole-5-thiol and partial de-blocking using phosphorous pentachloride converts exomethylene (V) into the nucleus (VI). Acylation of the nucleus with an appropriately blocked side-chain (VII) followed by final de-blocking using aluminum chloride gives moxalactam acid (VIII). 

So far, most microorganisms and enzymes derived therefrom have been used in the reduction of a single keto group of p-keto or a-keto compounds [68-71], Recently, Patel et al. [72] have demonstrated the stereoselective reduction of 3,5-dioxo-6-(benzyloxy)hexanoic acid, ethyl ester (41), to (3,S, 5R)-dihydroxy-6-(benzyloxy)hexanoic acid, ethyl ester (42a) (Fig. 14). The compound (42a) is a key chiral intermediate required for the chemical synthesis of [4-[4a,6P(E)]]-6-[4,4-bis(4-fluorophenyl)-3-(l-methyl-lH-tetrazol-5-yl)-l,3-butadienyl]-tetrahydro-4-hydroxy-2H-pyran-2-one, compound R-( + )-(43), a new anticholesterol drug that acts by inhibition of HMG CoA reductase [73], Among various microbial cultures evaluated for the stereoselective reduction of diketone (41), cell suspensions of Aci-... 

RN Patel, CG McNamee, LJ Szarka. Enantioselective enzymic acetylation of racemic [4-[4a,6P(E)]]-6-[4,4-bis(4-fluorophenyl)-3-(l-methyl-lH-tetrazol-5-yl)-l,3-butadienyl]tetrahydro-4-hydroxy-2H-pyran-2-one. Appl Microbiol Biotechnol 38 56-60, 1992. 

Chemical Name N-[l-[2-(4-Ethyl-4,5-dihydro-5-oxo-lH-tetrazol-l-yl)ethyl]-4-(methoxy-methyl)-4-piperidinyl]-N-phenylpropaneamide hydrochloride... 

Chemical Name Sodium 7-(D-2-formyloxy-2-phenylacetamido)-3-(l-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate... 

The reaction mixture was stirred for 1.5 hours at about room temperature after the addition of the mandeloyl chloride was completed. Five liters of water were then added to the reaction mixture and the diluted mixture was stirred for about 10 minutes. The organic layer was separated and was washed twice with water. The combined washes are extracted with 1.5 I of ethyl acetate and the extract is combined with the washed organic layer. The whole was dried over magnesium sulfate, filtered and evaporated in vacuo on a 25°C water bath to yield 1,460 g of product, 7-(D-2-formyloxy-2-phenylacetamido)-3-(l-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid, as a yellow foam. 

The product was dissolved in 5 I of acetone and the solution was mixed with a solution of 430 g (2.59 mols) of sodium 2-ethylhexanoate in 5.4 I of acetone. The combined solutions were seeded and stirred in an ice bath for 1.5 hours. The crystalline precipitate of sodium 7-(D-2-formyloxy-2-phenylacetamido)-3-(1-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate was filtered and washed with 5 I of acetone. The crystalline salt was dried overnight in a vacuum oven at 40°C to yield 1,060 g (80%)of product, melting at 182°C to 184°C. 

Chemical Name 7-[D-(-)-a-(4-Ethyl-2,3-dioxo-l-piperazinecarboxamido)-a-(4-hydroxyphenyl)acetamido]-3-[( 1-methyl-lH-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid... 

Chemical Name 7-[[Carboxy(4-hydroxyphenyl)acetyl]amino]-7-methoxy-3-[[(1-methyl-lH-tetrazole-5-yl)thio]-methyl]-8-oxo-5-oxa-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt... 

Deprotonation-silylation of 1-methyl-lH-tetrazole exhibits predominant C-silylation at the 5-position to form l-methyl-5-trimethylsilyl-lH-tetrazole (it is not a SMA, silylated carbon atom being sp2). When this position is blocked by a silyl or a phenyl group, silylation occurs on the /V-methyl to yield SMA derivatives.158... 

Dimethyl-5,5 -hydrazo-lH-tetrazole or 5,5 -Hydrazobis[l-methyl-l,2,3,4-tetrazole]... 

Cefminox. [6R-[6a,7thio]methyl]S-oxo-S-thia-I-azabicyc (o-[4.2.0]oct-2-ene-2-carboxytic add 7,5-t2-1 -amino -2-ea rb-oxyethy]thioacetamido)-7 -methoxy-3-[[(l -methyl-12f-tetrazol 5-yl)thio]methyl]-3-cephem -4 -carboxylic acid. C)6HnN707S3 mol wt 519.57. C 36.99%, H 4.07%, N 18.87%, O 21.56%, S 18.51 %. Semisynthetic broad spectrum cephamycin antibiotic. Prepn Belg. pat. 880,686, K. 

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