Structure of New 2‐Oxo‐2,8‐dihydro‐[l,2,4]oxadiazolo‐[2,3‐a]pyrimidinecarbamates

Müller, Jean-Claude; Rarouz, Henri; Daly, J. J.; Schönholzer, Peter

doi:10.1002/hlca.19820650519

Cited by 10 publications

(2 citation statements)

References 9 publications

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“…Unlike the literature structure of ethyl N -phenylcarbamate, where the C(aryl)−N bond (1.405(6) Å) is significantly longer than the C(carbonyl)−N bond (1.352(8) Å), the C(aryl)−N bond (1.381(4) Å) in 4 is essentially the same length as the C(carbonyl)−N bond (1.377(4) Å). This is also the case for another N -(2-pyrimidinyl)carbamate described in the literature 5 …”

supporting

confidence: 64%

Unusually Low Barrier to Carbamate C−N Rotation

et al. 2002

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The barrier for rotation about an N-alkylcarbamate C(carbonyl)-N bond is around 16 kcal/mol. In the case of an N-phenylcarbamate, the rotational barrier is lowered to 12.5 kcal/mol, but with N-(2-pyrimidyl)carbamates the barriers are so low (<9 kcal/mol) that the syn and anti rotamers cannot be observed as separate signals by 500 MHz NMR spectroscopy at 183 K. X-ray and computational data show that the N-(2-pyrimidyl) carbamates have C(carbonyl)-N bonds that are on average 0.03 A longer than for related N-phenylcarbamates. The computational results trace the origin of the effect to increased single bond character for the C(carbonyl)-N bond due to the increased electron-withdrawing ability of the pyrimidyl ring.

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confidence: 64%

Unusually Low Barrier to Carbamate C−N Rotation

et al. 2002

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“…In a series of reports, we recently described the synthesis of new 2-0x0-2H-[ 1, 2,4]oxadiazolo [2,3-a]pyrimidine-7-carbamates 1 [ 11 [2] and the synthesis of the regioisomers 2-0x0-2 H-[ 1, 2,4]oxadiazolo [2,3-c]pyrimidine-5-carbamates 2 [3], which both possess interesting cardiovascular properties. As a result of these investigations, l a (Ro 12-4713), a potent antihypertensive agent was chosen to undergo clinical trials.…”

mentioning

confidence: 99%

A New Route to the Synthesis of 2‐Amino‐6‐(methoxycarbonyl)amino‐4‐(tetrahydropyridyl)pyrimidine 1‐Oxide

Müller

Ramuz

Wagner

1983

Helvetica Chimica Acta

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SummaryA new approach to 2-amino-6-(methoxycarbonyl)amino-4-( 1,2,3,6-tetrahydro-1 -pyridyl)pyrimidine 1 -oxide (3) is described. Methyl [ l-ethoxy-2-(ethoxycarbonyl)-ethylidenelcarbamate (5) reacted with guanidine to the pyrimidinecarbamate 6, which was successively transformed into methyl 2-amino-6-@-tolylsulfonyl)oxy-4-pyrimidinecarbamate (8). Oxidation of 8 led to the corresponding pyrimidine Noxide 9, a useful starting material to 3.In a series of reports, we recently described the synthesis of new 2-0x0-2H-[ 1,2,4]oxadiazolo [2,3-a]pyrimidine-7-carbamates 1 [ 11 [2] and the synthesis of the regioisomers 2-0x0-2 H-[ 1,2,4]oxadiazolo [2,3-c]pyrimidine-5-carbamates 2 [3], which both possess interesting cardiovascular properties. As a result of these investigations, l a (Ro 12-4713), a potent antihypertensive agent was chosen to undergo clinical trials. One of the main metabolites of Ro 12-4713 in animals as well as in man was found to be the 2-amino-6-(methoxycarbonyl)amino-4-( 1,2,3,6-tetrahydro-1 -pyridyl)pyrimidine 1 -oxide (3) [4].To secure 3 in quantities sufficient for its biological evaluation and for its further transformation into 2, it was necessary to develop an alternative to the previously reported routes [l] [3].We describe here a new synthesis of 2,4,6-trisubstituted pyrimidine nucleus which allows introduction of the carbamate moiety in position 4 at an early stage, whereas the substitution with tetrahydropyridyl in position 6 is performed at the last step.Treatment of ethyl cyanoacetate with HC1 in EtOH gave the 3-amino-3-ethoxyacrylate hydrochloride 4. Transformation of 4 into the methyl carbamate 5 (mixture I )

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References

1987

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Structure of New 2‐Oxo‐2,8‐dihydro‐[l,2,4]oxadiazolo‐[2,3‐a]pyrimidinecarbamates

Abstract: SummaryThe structure of new 2-0~0-2,8-dihydro-[ 1,2,4]oxadiazolo-[2,3-a]pyrimidinecarbamates 1 was established by correlating the IR. and NMR. data with these of analogous compounds. A X-ray crystallographic analysis of l c gave an unequivocal proof of structural assignment.

Cited by 10 publications

References 9 publications

Unusually Low Barrier to Carbamate C−N Rotation

Unusually Low Barrier to Carbamate C−N Rotation

A New Route to the Synthesis of 2‐Amino‐6‐(methoxycarbonyl)amino‐4‐(tetrahydropyridyl)pyrimidine 1‐Oxide

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