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D. Castagnolo et al.
LETTER
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(10) Synthesis of 2-Aminothiazoles 9a–i; General Procedure:
Alkyne 3, 6 or 7 (1.0 mmol) and the appropriate thiourea 8a–
c (1.0 mmol) were suspended in anhyd DMF (1.0 mL) in a
10 mL glass vial equipped with a small magnetic stirring bar.
K2CO3 (1.0 mmol) was then added to this solution and the
mixture was irradiated under microwave conditions at
130 °C (2 × 5 min), using an irradiation power of 300 W.
Microwave irradiations were conducted using a CEM
Discover Synthesis Unit (CEM Corp., Matthews, NC). The
mixture was then poured into H2O (10 mL) and then
extracted with EtOAc (2 × 10 mL). The combined organic
phases were washed with brine, dried over Na2SO4, filtered
and concentrated under reduced pressure. The crude
products were purified by flash column chromatography
(SiO2; hexanes–EtOAc, 1:1), to yield the 2-aminothiazoles
9a–i as tan-colored oils.
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(11) Characterization of 13a: 1H NMR (CDCl3): d = 7.54 (s, 1 H,
SCHCHCH3), 7.08–7.06 (m, 1 H, Ph), 6.75–6.71 (m, 2 H,
Ph), 4.56–4.54 (m, 1 H, CH3CHPh), 2.34 (s, 3 H, NCCH3),
1.94 (s, 3 H, CH3), 1.58 (d, 3 H, CHCH3). 13C NMR
(CDCl3): d = 162.61, 160.13, 159.36, 151.22, 128.20,
128.00, 124.85, 119.38, 117.84, 111.64, 34.27, 17.88, 13.47,
10.35. MS (ESI): m/z = 321 [M + H]+, 343 [M + Na]+.
Characterization of 13b: 1H NMR (CDCl3): d = 7.08–7.04
(m, 1 H, Ph), 6.76–6.72 (m, 2 H, Ph), 6.27 (s, 1 H,
SCHCHCH3), 4.54–4.49 (m, 1 H, CH3CHPh), 2.70 (s, 3 H,
NCCH3), 1.89 (s, 3 H, CH3), 1.58 (d, 3 H, CHCH3). 13
C
NMR (CDCl3): d = 162.63, 162.24, 160.14, 146.41, 135.98,
128.09, 119.37, 112.86, 111.38, 105.68, 34.07, 18.56, 17.77,
10.23. MS (ESI): m/z = 321 [M + H]+, 343 [M + Na]+.
(12) Characterization of 14: 1H NMR (CDCl3): d = 7.11–7.04
(m, 3 H, Ph), 6.81–6.72 (m, 4 H, Ph), 5.97 (s, 1 H, SCH),
4.53 (m, 1 H, CH3CHPh), 4.50 (s, 2 H, CH2PhOMe), 3.71
(s, 3 H, OCH3), 1.91 (s, 3 H, CH3), 1.59 (d, J = 8.0 Hz,
3 H, CHCH3). 13C NMR (CDCl3): d = 162.60, 161.85,
160.35, 158.61, 140.31, 130.62, 130.38, 129.99, 119.34,
114.38, 113.84, 111.77, 111.30, 106.19, 55.40, 37.06, 33.96,
17.80, 10.77. MS (ESI): m/z = 427 [M + H]+, 449 [M + Na]+.
(6) Dai, W.; Petersen, J. L.; Wang, K. K. Org. Lett. 2006, 8,
4665.
(7) Reaction of alkyne 7 with thiourea 8a was also carried out
under the same reaction conditions but in the absence of
K2CO3. No traces of aminothiazole 9g were detected in this
case and only complex side products, whose characterization
was difficult, were isolated.
Synlett 2009, No. 13, 2093–2096 © Thieme Stuttgart · New York