Process for preparing N-tert-butyl-2-pyrazinecarboxamide and N-t

Details Process for preparing N-tert-butyl-2-pyrazinecarboxamide and N-t Process for preparing N-tert-butyl-2-pyrazinecarboxamide and N-t

1995-07-20

1998-03-31

Bernhardt, Emily

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

544390, C07D24104, C07D24114

Patent

active

057340552

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a process for preparing a N-tert-butyl-2-pyrazinecarboxamide and a N-tert-butyl-2-piperazinecarboxamide which are useful as intermediates of medicines.


BACKGROUND OF ARTS

A N-tert-butyl-2-pyrazinecarboxamide is a known compound, and reactions in which this compound is used as a starting substance are already known. There is, however, no report concerning a process for preparing a N-tert-butyl-2-pyrazinecarboxamide.
Also, it is shown in Japanese Unexamined Patent Publication No. 117869/1989 that a N-tert-butyl-2-piperazinecarboxamide, which is one of the compounds obtained by the preparation process of the present invention, can be obtained by hydrogenation of a N-tert-butyl-2-pyrazinecarboxamide.
However, in the above-mentioned process, expensive platinum oxide is used as a catalyst, and the reaction of hydrogenation has to be performed under the high pressure of 100 atm (1.01.times.10.sup.4 kPa) for 6 hours; therefore, the process is not necessarily advantageous for a manufacture on an industrial basis.
An object of the present invention is to obtain a N-tert-butyl-2-pyrazinecarboxamide, which is useful as an intermediate of medicines, in a high yield. The other object of the present invention is to provide a process for preparing a N-tert-butyl-2-piperazine-carboxamide which is useful as an intermediate of medicines by performing hydrogenation of a N-tert-butyl-2-pyrazinecarboxamide under economical and industrially advantageous conditions.


DISCLOSURE OF THE INVENTION

The present inventors had investigated various things to solve the above problems. As a result of the investigation, they found the following facts and completed the present invention: a N-tert-butyl-2-pyrazinecarboxamide can be obtained in a high yield by the reaction of a cyanopyrazine with a tert-butyl alcohol in the presence of sulfuric acid; additionally, a N-tert-butyl-2-piperazinecarboxamide can be prepared a high yield, unexpectedly under a pressure which low enough to easily manage for a manufacture on an industrial basis and for a short reaction time, by hydrogenation of the above-mentioned N-tert-butyl-2-pyrazinecarboxamide using inexpensive Raney nickel or Raney cobalt as a catalyst.
Namely, the present invention relates to formula (2): ##STR4## wherein R.sup.1 and R.sup.2 are the same or different from each other and each represents an alkyl group or hydrogen; Bu.sup.t represents tert-butyl group, which comprises reacting a cyanopyrazine having the formula (1): ##STR5## wherein R.sup.1 and R.sup.2 are the same as the above, with tert-butyl alcohol in the presence of sulfuric acid; formula (3): ##STR6## wherein R.sup.1, R.sup.2 and Bu.sup.t are the same as the above, which comprises hydrogenating of a N-tert-butyl-2-pyrazinecarboxamide having the formula (2): ##STR7## wherein R.sup.1, R.sup.2 and Bu.sup.t are the same as the above, in the presence of Raney nickel or Raney cobalt; and the formula (3): ##STR8## wherein R.sup.1, R.sup.2 and Bu.sup.t are the same as the above, which comprises reacting in that a cyanopyrazine having the formula (1): ##STR9## wherein R.sup.1 and R.sup.2 are the same as the above, with tert-butyl alcohol in the presence of sulfuric acid to prepare a N-tert-butyl-2-pyrazinecarboxamide having the formula (2): ##STR10## wherein R.sup.1, R.sup.2 and Bu.sup.t are the same as the above, and hydrogenating of said N-tert-butyl-2-pyrazinecarboxamide in the presence of Raney nickel or Raney cobalt.
In the above-mentioned processes, it is preferable that 2 to 5 moles of sulfuric acid is used to one mole of a cyanopyrazine having the formula (1), and that the reaction is performed at 0.degree. to 50.degree. C. Further, it is preferable that the above-mentioned hydrogenation is performed at 70.degree. to 130.degree. C.
In order to perform the process of the present invention for preparing a N-tert-butyl-2-pyrazine-carboxamide having the formula (2), tert-butyl alcohol may be added dropwise to the mixture of sulfuric acid and a cyanopyrazine having the formula

REFERENCES:
patent: 5463067 (1995-10-01), Askin et al.
Sato et al, J. Chem. Soc. Perkin Tans. I, pp. 2877-2881 (1991).
Barlin, The Pyrazine, pp. 275-279 (1982).
Organic Syntheses (John Wiley & Sons, Publishers), Collective vol. 5, pp. 73-75 (1973).
Schumacher et al, J. Org. Chem, 54, pp. 2242-2244.
Y. Ito et al. 2(Aminomethyl)piperazine derivatives as intermediates for drugs. Chemical Abstracts, No. 232862w -- vol. III 1989.
CA, vol. 105:190963y, p. 717, 1986 and the corresponding Japanese Unexamined Patent Publication No. 151174/1986.
CA, vol. 107:236524c, p. 771, 1987 and the corresponding Japanese Unexamined Patent Publication No. 198662/1987, Sep. 2, 1987.

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