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Molbank 2007, M545 |
3-tert-butoxycarbonylamino-pyridine-2-carboxylic Acid Methyl Ester
Rachid Mamouni a,c,*, Mohammadine El Haddad b,c and Mohamed Akssira c
a Faculté des Sciences, Université Ibn
Zohr, BP 8061, 8000, Agadir,
Morocco
b Faculté Poly-disciplinaire de Safi, Université
Cadi Ayyad, BP 4162, 46 000
c Laboratoire de Chimie Bioorganique & Analytique, FSTM, Université
Hassan II -Mohammedia,BP 146, 20 800 Mohammedia, Morocco
* Author to whom correspondence should be addressed. Fax: +(212) 048220100; E-mail: [email protected]
Received: 23 January 2006 / Accepted: 24 February 2006 /
Published: 30 May 2007
Keywords: Curtius
rearrangement, Pyridopyrimidine,
bioactivity
The
discussion and purpose for the synthesis of the 2,
3-pyridinecarboxylicacid-2-methylester 1
has been reported elsewhere [1]. To a solution of half-ester (1.0 g,
5.52 mmol) in dry tetrahydrofuran
(15 ml) cooled at –10°C was added drop-wise triethylamine
(1.52 ml, 11.04 mmol) then ethyl chloroformate
(0.79 ml, 8.28 mmol). The mixture was stirred for 30
minutes at –10°C. Analysis by tlc
showed complete conversion to a very non-polar product. A solution of sodium azide (0.61 g, 9.38 mmol) in
water (4 ml) was then added drop wise continued stirring for 1h at –10°C. The
resulting mixture was filtered, evaporated and the aqueous phase was extracted
with ethyl acetate (3 x 15 ml). The combined organic layer were washed with
brine, dried (MgSO4), filtered and concentrated in vacuo. The acyle azide was slowly brought to reflux in toluene for 2h to
give by Curtius rearrangement cleanly isocyanate. The subsequent reaction of isocyanate with 2-Methyl-2-propanol at 100°C for 3 hours.
After evaporation in vacuo, the crude product was
purified by chromatography on silica gel (9/1 : EtOAc/petroleum ether) to give 3-tert-Butoxycarbonylamino-pyridine-2-carboxylic
acid methyl ester 2 (1.03 g, 80%).
Rf: 0.36 (9:1, EtOAc/petroleum
ether)
Melting
point: 94°C (pale white crystals, from hexane)
IR
(KBr,υ, cm-1): 3298, 3000
(NH), 1721, 1691 (CO).
1H-NMR (300 MHz, DMSO-d6,
δ, ppm): 1.47 (s, 9H, CH3), 3.85 (s, 3H,
CH3), 7.55 ( dd, 1H, J = 8.5, 4.3
Hz, H-5), 8.32 (dd, 1H, J = 4.3, 1.3 Hz, H-4),
8.41 (dd, 1H, J = 8.5, 1.3, H-6), 9.90 (s, 1H,
NH).
13C- NMR (75 MHz, DMSO-d6,
δ, ppm): 27.82 (3CH3), 52.44 (CH3O),
80.62 (C(CH3)3), 127.54, 127.71,
134.25, 137.28, 142.25, 152.17, 167.00 (CO).
MS
m/z: 253 [M+1], 197.5, 165.0, 153.0, 139.0, 121.5.
Elemental analysis: Calculated C12H16 N2O4:
C, 57.13; H, 6.39; N, 11.10 Found: C, 57.21; H, 6.45;
N, 11.07.
Acknowledgements
We
wish to thank the ministry ESRSFC of the Moroccan Government (PROTARS-P2T2/07)
for financial support.
References
1. Mamouni, R.; Aadil, M.; Akssira, M.; Lasri, J.; Sepulveda-Arques, J. Tetrahedron Lett. 2003, 44, 2745-2747.
© 2007 by MDPI (http://www.mdpi.org/). Reproduction is permitted for noncommercial purposes.