T. J. J. Mꢀller et al.
5.00 mmol), and dry triethylamine (1.39 mL, 10.0 mmol) were successive-
ly added to the mixture and stirring at room temperature was continued
for 1 h. The evolution of CO can be observed. After complete conversion
(monitored by TLC) saturated brine (25 mL) was added, and the mixture
was extracted with dichloromethane (3ꢃ25 mL). The combined organic
layers were dried with anhydrous sodium sulfate. After removal of the
solvents in vacuo the residue was absorbed onto Celite and chromato-
graphed on silica gel with hexanes/ethyl acetate to give the alkynone 3b
(1.17 g, 74%) as a yellow solid. M.p. 84–858C; 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=8.44–8.38 (m, 1H), 7.90 (s, 1H), 7.39–7.13 (m,
8H), 5.35 (s, 2H), 2.44 (t, J=7.5 Hz, 2H), 1.62 (quint, J=8.3 Hz, 2H),
1.47 (sext, J=8.3 Hz, 2H), 0.94 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=171.8 (Cquat), 138.1 (CH), 137.3 (Cquat),
135.5 (Cquat), 129.1 (CH), 128.3 (CH), 127.1 (CH), 126.1 (Cquat), 123.8
(CH), 123.0 (CH), 122.6 (CH), 118.9 (Cquat), 110.3 (CH), 91.0 (Cquat), 80.6
(Cquat), 50.9 (CH2), 30.0 (CH2), 22.1 (CH2), 18.7 (CH2), 13.6 ppm (CH3);
EI+MS: m/z (%): 315 (100) [M+], 91 (40) [C7H7+]; IR (KBr): n˜ =730,
752, 771, 827, 1027, 1184, 1237, 1360, 1386, 1440, 1453, 1465, 1486, 1495,
1522, 1576, 1607, 2226, 2870, 2932, 2955 3119 cmÀ1; elemental analysis
calcd (%) for C22H21NO: C 83.78, H 6.71, N 4.44; found: C 83.64, H 6.71,
N 4.43.
Table 3. (Continued)
Entry
Ynone 3 or 9
2-Amino pyimindine 11 (isolated yield/%)
9
3i
11h (86)
10
11
9a
9b
11i (92)
11j (94)
[a] The reactions were performed at cACTHNUGTRNEUNG(3 or 9)=0.2m in 2-methoxyetha-
2-Aminopyrimidine 11b: In a screw-cap vessel under argon the alkynone
3b (315 mg, 1.00 mmol) was dissolved in 2-methoxyethanol (5 mL).
Then, potassium carbonate (346 mg, 2.50 mmol), and guanidinium hydro-
chloride (10) (239 mg, 2.50 mmol) were added and the mixture was
stirred at 1208C over night. Then, after cooling to room temperature sa-
turated brine (20 mL) was added, and the mixture was extracted with di-
chloromethane (5ꢃ20 mL). The combined organic layers were dried with
anhydrous sodium sulfate. After removal of the solvents in vacuo the res-
idue was absorbed onto Celite and chromatographed on silica gel with di-
chloromethane and dichloromethane/methanol/aqueous ammonia
(100:1:1) to give the 2-amino pyrimidine 11b (305 mg, 86%) as a pale
yellow solid. M.p. 174–1758C; 1H NMR (300 MHz, CDCl3, 278C, TMS):
d=8.40–8.33 (m, 1H), 7.84 (s, 1H), 7.35–7.18 (m, 6H), 7.18–7.11 (m,
2H), 6.89 (s, 1H), 5.35 (s, 2H), 5.05 (s, 2H, NH2), 2.60 (t, J=7.5 Hz, 2H),
1.72 (quint, J=7.5 Hz, 2H), 1.42 (sext, J=7.5 Hz, 2H), 0.95 ppm (t, J=
7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, 278C, TMS): d=171.4 (Cquat),
163.1 (Cquat), 162.5 (Cquat), 137.4 (Cquat), 136.5 (Cquat), 130.3 (CH), 128.9
(CH), 127.9 (CH), 126.9 (CH), 126.3 (Cquat), 122.6 (CH), 121.7 (CH),
121.2 (CH), 114.8 (Cquat), 110.3 (CH), 106.4 (CH), 50.5 (CH2), 37.8 (CH2),
31.2 (CH2), 22.6 (CH2), 14.0 ppm (CH3); EI+MS: m/z (%): 356 (27) [M+
], 341 (3) [M+ÀCH3], 268 (7) [M+ÀC2H5], 314 (100) [M+ÀC3H6], 223
(5) [M+ÀC10H13], 91 (14) [C7H7+]; IR (KBr): n˜ =743, 1175, 1385, 1456,
1469, 1521, 1577, 1628, 1645, 2860, 2927, 2956, 3442, 3463 cmÀ1; elemental
analysis calcd (%) for C23H24N4: C 77.50, H 6.79, N 15.72; found: C
77.45, H 6.75, N 15.77.
nol. [b] TMS and TIPS were deprotected in the course of the reaction.
Figure 2. Molecular structure of 2-amino pyrimidine 11b (hydrogen
atoms were omitted for clarity).
vast potential to diversity-oriented syntheses of heterocycles.
Studies expanding the scope of this novel access to alky-
nones and their elaboration towards multi-component syn-
theses of heterocycles are currently underway. In addition,
the stage has been set for the methodological expansion to
further decarbonylative cross-couplings that are currently
under investigation.
Acknowledgements
This work was supported by Merck Serono, Darmstadt, and the Fonds
der Chemischen Industrie.
À
Keywords: acylation
multicomponent reactions · pyrimidines
·
alkynones
·
C C coupling
·
Experimental Section
General methods and further reactions are given in the Supporting Infor-
mation.
[1] For a review, see e.g. R. A. Bol’shedvorskaya, L. I. Vereshchagin,
Russ. Chem. Rev. 1973, 42, 225–240.
Three-component synthesis of alkynone 3b: N-Benzyl-1H-indole (7a)
(1.04 g, 5.00 mmol) in dry THF (25 mL) was placed under argon in a
screw-cap vessel with septum, degassed with argon and cooled to 08C
(water/ice). Then, oxalyl chloride (0.44 mL, 5.00 mmol) was added to the
reaction mixture at 08C. The mixture was allowed to come to room tem-
perature and was stirred for 4 h. Then, [PdCl
0.05 mmol), CuI (10 mg, 0.05 mmol), 1-hexyne (2a) (0.59 mL,
2ACHTUNGTRNEN(UNG PPh3)2] (35 mg,
5010
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 5006 – 5011