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resulting reaction mixture was stirred at 25 °C for 24 h. Then, the
reaction mixture was concentrated under vacuum to afford N-sub-
stituted α-aminoamide 8 without further purification.
2-(4-Chlorobenzylamino)acetamide (8a): Following the general
procedure, the reaction of ethyl (4-chlorobenzyl)glycinate (3p,
150 mg, 0.66 mmol) with ammonia gas in methanol (5.0 mL) at
25 °C for 24 h afforded compound 8a as a white solid (127 mg,
97 %), m.p. 103–105 °C (amorphous).[2f] 1H NMR (400 MHz, CDCl3):
δ = 1.85 (br. s, 1 H), 3.29 (s, 2 H), 3.77 (s, 2 H), 5.86 (br. s, 1 H), 6.94 (br.
s, 1 H), 7.23–7.32 (m, 4 H) ppm. HRMS (ESI+): calcd. for C9H12ClN2O+
199.0638 [M + H]+, found 199.0625.
[3]
2-(Phenylamino)acetamide (8b): Following the general procedure,
the reaction of ethyl phenylglycinate (6k, 150 mg, 0.84 mmol) with
ammonia gas in methanol (5.0 mL) at 25 °C for 24 h afforded com-
pound 8b as a light-brown solid (124 mg, 99 %), m.p. 135–136 °C
(amorphous).[51] 1H NMR (400 MHz, CDCl3): δ = 3.80 (d, J = 5.6 Hz,
2 H), 4.30 (br. s, 1 H), 5.66 (br. s, 1 H), 6.58 (br. s, 1 H), 6.64 (d, J =
7.6 Hz, 2 H), 6.82 (t, J = 7.4 Hz, 1 H), 7.22 (t, J = 7.5 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 48.4 (CH2), 113.1 (CH), 119.2 (CH),
129.5 (CH), 146.9 (C), 173.5 (C) ppm. HRMS (ESI+): calcd. for
C8H11N2O+ 151.0871 [M + H]+, found 151.0853.
[4]
[5]
[6]
[7]
General Procedure for the Synthesis of 7-Phenyl-7H-purine 11:
A solution of the 2-(phenylamino)acetonitrile 6l (50 mg, 0.38 mmol)
and formamidine acetate 9 (236 mg, 2.27 mmol) in n-butanol
(2.0 mL) was irradiated with microwaves at 140 °C for 2 × 15 min in
a sealed tube containing a teflon-coated magnetic stirring bar. The
formamidine acetate was added in two equal portions involving
two heating/cooling cycles. The resulting reaction mixture was
cooled to 55 °C, concentrated and the residue taken up in water.
This was extracted with CH2Cl2 (2 × 5.0 mL) and the combined or-
ganic layers were dried with anhydrous sodium sulfate, filtered and
concentrated under vacuum to give the crude product. Column
chromatography (CH2Cl2/MeOH, 25:1) on silica gel of this material
afforded compound 11 (22 mg, 30 %) as a white solid, m.p. 185–
186 °C (amorphous).[29] 1H NMR (400 MHz, CDCl3): δ = 7.53–7.67
(m, 5 H), 8.47 (s, 1 H) 9.07 (s, 1 H), 9.22 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 123.5 (CH), 125.2 (C), 129.3 (CH), 130.6 (CH),
134.8 (C), 140.7 (CH), 146.8 (CH), 153.8 (CH), 161.1 (C) ppm. HRMS
[8]
[9]
[10]
[11]
(ESI+): calcd. for C11H9N4 197.0827 [M + H]+, found 197.0809.
+
[12]
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Acknowledgments
The authors are grateful for the financial support from the Uni-
versidad de los Andes and COLCIENCIAS. J. O.-H. also is grateful
to the Department of Chemistry at Universidad de los Andes
for her doctoral scholarship. Edwin Guevara is acknowledged
for acquiring the mass spectra.
Keywords: Synthetic methods · N-Alkylation ·
Chemoselectivity · C–N bond formation · Secondary
amines · Cesium
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