3122
D. S. Ermolat’ev et al.
LETTER
d = 7.65 (d, J = 8.2 Hz, 2 H), 7.33 (m, 5 H), 7.17 (s, 1 H),
was subjected to silica gel flash chromatography (from 10%
to 50% CH2Cl2 in PE) to afford compounds 5a–g.
6.93 (d, J = 8.2 Hz, 2 H), 5.04 (s, 2 H), 3.82 (s, 3 H). 13
C
NMR (75 MHz, CDCl3): d = 160.6, 155.2, 141.2, 133.1,
130.9, 130.4, 128.9, 127.1, 126.5, 126.2, 121.8, 115.2, 99.1,
85.9, 55.8, 53.0. HRMS (EI): m/z calcd for C20H15ClN2O2:
350.0822; found: 350.0831.
2-(4-Chlorophenyl)-6-propylfuro[2,3-b]pyrazine (5a)
Yield 81%; mp 143–144 °C. H NMR (300 MHz, CDCl3):
1
d = 8.55 (s, 1 H), 8.94 (d, J = 8.3 Hz, 2 H), 7.48 (d, J = 8.3
Hz, 2 H), 6.65 (s, 1 H), 2.87 (d, J = 7.5 Hz, 2 H), 1.86 (m, 2
H), 1.06 (d, J = 7.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
d = 166.2, 154.7, 148.6, 141.9, 135.7, 135.3, 134.1, 129.4,
129.1 (2×), 128.3 (2×), 103.8, 31.2, 20.6, 13.7. HRMS (EI):
m/z calcd for C15H13ClN2O: 272.0716; found: 272.0708.
(20) For use of tetrabutylammonium bromide additive in
Buchwald–Hartwig amination, see: (a) Mei, X.; Martin, R.
M.; Wolf, C. J. Org. Chem. 2006, 71, 2854. (b) Mei, X.;
Wolf, C. Tetrahedron Lett. 2006, 47, 7901. (c) Mei, X.;
Martin, R. M.; Wolf, C. J. Am. Chem. Soc. 2006, 128, 13326.
(21) For reports of microwave-promoted amination, see:
(a) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.;
Dommisse, R. Tetrahedron 2001, 57, 7027. (b) Sharifi, A.;
Hosseinzadeh, R.; Mirzaei, M. Monatsh. Chem. 2002, 133,
329. (c) Wan, Y.; Alterman, M.; Hallberg, A. Synthesis
2002, 1597. (d) Wang, T.; Magnin, D. R.; Hamann, L. G.
Org. Lett. 2003, 6, 897. (e) Maes, B. U. W.; Loones, K. T.
J.; Hostyn, S.; Diels, G.; Rombouts, R. Tetrahedron 2004,
60, 11559. (f) Loones, K. T. J.; Maes, B. U. W.; Rombouts,
G.; Hostyn, S.; Diels, G. Tetrahedron 2005, 61, 10338.
(22) Typical Procedure for the Preparation of Furopyrazines
5h–l
(17) Typical Procedure for the Preparation of Furopyrazines
4a–m
In a 25 mL flask pyrazinone 3 (2 mmol) was dissolved in
anhyd CH2Cl2 (12 mL). Then, AgOTf (11 mg, 2 mol%) and
TFA (0.8 mL, 10 mmol, 5 equiv) were added and the
reaction mixture was stirred at r.t. for 5–20 min. After
reaction completion the solvent was evaporated and the
residue was subjected to silica gel column chromatography
(from 20% to 50% CH2Cl2 in PE) to afford compounds
4a–m.
2-Chloro-6-phenylfuro[2,3-b]pyrazine (4a)
Yield 91% yield; mp 174–176 °C. 1H NMR (300 MHz,
CDCl3): d = 8.21 (s, 1 H), 7.95 (d, J = 8.3 Hz, 2 H), 7.53 (m,
3 H), 7.17 (s, 1 H). 13C NMR (75 MHz, CDCl3): d = 162.3,
154.6, 146.0, 142.1, 136.6, 131.3, 129.6, 128.8, 126.2,
101.2. HRMS (EI): m/z calcd C12H7ClN2O: 230.0247;
found: 230.0246.
(18) For reports of microwave-promoted Suzuki couplings in
organic solvents or solvent-free, see: (a) Hallberg, A.;
Larhed, M. J. Org. Chem. 1996, 61, 9582. (b) Wang, Y.;
Sauer, D. R. Org. Lett. 2004, 6, 2793. (c) Kabalka, G. W.;
Wang, L.; Pagni, R. M.; Hair, C. M.; Namboodiri, V.
Synthesis 2003, 217. (d) Kabalka, G. W.; Pagni, R. M.;
Wang, L.; Namboodiri, V.; Hair, C. M. Green Chem. 2000,
2, 120. (e) Appukkuttan, P.; Orts, A. B.; Chandran, R. P.;
Goeman, J. L.; Van der Eycken, J.; Dehaen, W.; Van der
Eycken, E. Eur. J. Org. Chem. 2004, 15, 3277.
In a 15 mL microwave vial were successively dissolved, in
1,4-dioxane (4 mL), furopyrazine 4 (0.5 mmol), amine 6
(0.63 mmol, 1.25 equiv), Pd(OAc)2 (3.5 mg, 3 mol%), and
( )-BINAP (11 mg, 3.3 mol%), tetrabutylammonium
bromide (1.0–1.2 equiv), and NaOt-Bu (1.5–1.7 equiv). The
reaction tube was sealed and irradiated in the cavity of a
Milestone-MYCROSYNTH multimode reactor at a ceiling
temperature of 120 °C at 300 W maximum power for 15
min. After the reaction mixture was cooled with an airflow
for 15 min, then it was extracted with CH2Cl2 (2 × 50 mL)
and dried over MgSO4. The solvent was removed under
reduced pressure and the residue was subjected to silica gel
flash chromatography (from 10% to 30% EtOAc in PE) to
afford compounds 5h–l.
2-Morpholin-4-yl-6-phenylfuro[2,3-b]pyrazine (5h)
Yield 91%; mp 95–97 °C. 1H NMR (300 MHz, CDCl3): d =
7.91 (d, J = 8.3 Hz, 2 H), 7.76 (s, 1 H), 7.46 (m, 3 H), 7.03
(s, 1 H), 3.89 (t, J = 4.6 Hz, 4 H), 3.57 (t, J = 4.6 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = 159.9, 155.2, 151.1, 130.3,
129.9, 129.4 (2×), 125.8 (2×), 124.4, 101.3, 67.1, 46.7.
HRMS (EI): m/z calcd for C16H15N3O2: 281.1164; found:
281.1174.
(f) Appukkuttan, P.; Dehaen, W.; Van der Eycken, E. Org.
Lett. 2005, 7, 2723. (g) Appukkuttan, P.; Dehaen, W.; Van
der Eycken, E. Comb. Chem. High Throughput Screening , ,
accepted. (h) Appukkuttan, P.; Dehaen, W.; Van der
Eycken, E. Chem. Eur. J. 2007, 13, 6452.
(19) Typical Procedure for the Preparation of Furopyrazines
5a–g
In a 15 mL microwave vial were successively dissolved, in
DMF–H2O (1:1, 6 mL), furopyrazine 4 (0.7 mmol), boronic
acid 6 (0.86 mmol, 1.25 equiv), Pd(PPh3)4 (8 mg, 1 mol%),
and Na2CO3 (150 mg, 2 equiv). The reaction tube was sealed
and irradiated in the cavity of a Milestone-MYCROSYNTH
multimode reactor at a ceiling temperature of 100 °C at 100
W maximum power for 10 min. After the reaction mixture
was cooled with an airflow for 15 min, then it was extracted
with CH2Cl2 (2 × 50 mL) and dried over MgSO4. The
solvent was removed under reduced pressure and the residue
Synlett 2007, No. 20, 3117–3122 © Thieme Stuttgart · New York