The Journal of Organic Chemistry
Page 12 of 21
This compound 7 (220 mg, 307.1 ꢀmol) in anhydrous degassed 1,4ꢀdioxane (1.53 mL) was added degassed H2O (505 ꢀL),
K2CO3 (29.7 mg, 215.0 ꢀmol), vinylboronic anhydride pyridine complex (51.7 mg, 215.0 ꢀmol), PdCl2(PPh3)2 (21.5 mg,
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o
30.7 ꢀmol), and the mixture was stirred for 1 h under argon at 120 C. After the reaction mixture was diluted with EtOAc,
the organic layer was washed with brine, dried over Na2SO4, filtered and evaporated. Obtained crude material was purified
by silica gel column chromatography (eluent: hexane/ EtOAc, from 7: 1 to 4:1) to give compound 8 as a yellow form with a
+
slight amount of inpurity. HRMS (ESI) m/z: calcd. for C29H49N4O4Si2 [M+H]+ m/z 573.3287, m/z found 573.3302.
Obtained material was subsequently used to the next reaction. The vinyl derivative was dissolved in anhydrous 1,4ꢀdioxane
(1.23 mL) and NaSMe (43.4 mg, 605.3 ꢀmol) and H2O (417 ꢀL) was added. After stirring for 3 h at ambient temperature
and the reaction mixture was diluted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4,
filtered and evaporated, which afforded compound 8 as an pure yellow form (142 mg, 95%). 1HꢀNMR (600 MHz, CDCl3): δ
7.40 (s, 1H, 8ꢀH), 6.23 (d, 1H, J = 3.6 Hz), 4.82 (br, 2H), 4.46ꢀ4.45 (t, 1H, J = 5.4 Hz), 4.02ꢀ3.99 (m, 1H), 3.93ꢀ3.91 (dd,
1H, J = 3.0 Hz, 11.4 Hz), 3.80ꢀ3.78 (t, 1H, J = 4.2 Hz), 3.76ꢀ3.74 (dd, 1H, J = 2.4 Hz, 12Hz), 3.46 (s, 3H), 3.41ꢀ3.35 (m,
2H), 2.92ꢀ2.90 (m, 2H), 2.20 (s, 3H), 2.08 (s, 3H), 0.96 (s, 9H), 0.92 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H), 0.11 (s, 3H), 0.10 (s,
3H); 13CꢀNMR (150 MHz, CDCl3): δ 163.2, 159.4, 152.2, 125.8, 111.0, 97.8, 87.4, 85.5, 84.2, 84.1, 73.0, 69.8, 61.9, 58.4,
34.5, 33.2, 26.1, 25.8, 18.5, 18.2, 15.5, 4.6, ꢀ4.6, ꢀ4.8, ꢀ5.4, ꢀ5.5; HRMS (ESI) m/z: calcd for C30H53N4O4SSi2+ [M+H]+ m/z
621.3321, m/z found 621.3334.
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Synthesis
of
2ꢀPhenoxyacetylaminoꢀ5-propynylꢀ4ꢀ(2ꢀmethylthioethyl)ꢀ7ꢀ[(2ꢀOꢀmethylꢀ3,5ꢀOꢀtꢀbutyldimethylsilyl)
ꢀβꢀDꢀribofuranosyl)]ꢀ7Hꢀpyrroloꢀ[2,3ꢀd]pyrimidine (9)
To a solution of compound 8 (142 mg, 228.9 ꢀmol) in anhydrous pyridine (1.8 mL) was added phenoxyacetyl chloride (47
o
ꢀL, 343.4 ꢀmol) at 0 C, and stirred for 2h at ambient temperature, then diluted with ethyl acetate. The separated organic
layer was washed with brine, dried over Na2SO4, filtered, and evaporated. Obtained crude material was purified by silica gel
column chromatography to give compound 9 as a white form (151 mg, 87%). 1HꢀNMR (400 MHz, CDCl3): δ 8.80 (br, 1H),
7.79 (s, 1H), 7.38ꢀ7.34 (t, 2H, J = 7.6 Hz), 7.06ꢀ7.03 (m, 3H), 6.36 (d, 1H, J = 2.8 Hz), 4.82 (br, 2H), 4.50ꢀ4.48 (t, 1H, J =
4.8 Hz), 4.10ꢀ4.04 (m, 2H), 3.89ꢀ3.81 (m, 2H), 3.60 (s, 3H), 3.56ꢀ3.51 (m, 2H), 3.04ꢀ3.00 (t, 2H, J = 7.8 Hz), 2.22 (s, 3H),
2.10 (s, 3H), 1.00 (s, 9H), 0.93 (s, 9H), 0.18 (s, 3H), 0.17 (s, 3H), 0.12 (s, 3H), 0.11 (s, 3H); 13CꢀNMR (150 MHz, CDCl3): δ
163.4, 157.3, 151.4, 105.2, 129.8, 129.6, 128.8, 122.1, 114.9, 114.7, 97.7, 88.1, 86.3, 84.4, 84.0, 72.4, 69.2, 68.0, 61.5, 58.4,
+
34.2, 33.0, 26.1, 25.8, 18.5, 18.2, 15.6, 4.5, ꢀ4.6, ꢀ4.8, ꢀ5.40, ꢀ5.43;HRMS (ESI) m/z: calcd for C38H59N4O6SSi2 [M+H]+
m/z 755.3688, found m/z 755.3697.
Synthesis
of
2ꢀPhenoxyacetylaminoꢀ5-propynylꢀ4ꢀ(2ꢀmethylthioethyl))ꢀ7ꢀ[(2ꢀOꢀmethylꢀβꢀDꢀribofuranosyl)]ꢀ
7Hꢀpyrroloꢀ[2,3ꢀd]pyrimidine (10)
To a solution of 9 (150 mg, 198.8 ꢀmol) in anhydrous THF solution (225 ꢀL) was added 1.0 M tetrabutylammonium
fluoride in THF solution (596.5 ꢀmol, 597 ꢀL) at 0 °C, and the mixture was stirred for 1 h at ambient temperature. The
reaction mixture was concentrated under reduced pressure and obtained crude material was purified by silica gel column
1
chromatography (eluent: EtOAc/hexane, from 4:1 to 100:0) to give the compound 10 (87 mg, 83%). HꢀNMR (600 MHz,
CDCl3); δ 8.94 (br, 1H), 7.36ꢀ7.33 (m, 2H), 7.30 (s, 1H), 7.06ꢀ7.03 (m, 3H), 5.83 (d, 1H, J = 5.4 Hz), 4.72 (br, 2H),
4.67ꢀ466 (m, 2H), 4.24 (m, 1H) , 4.20 (m, 1H), 3.99ꢀ3.97 (m, 1H), 3.86ꢀ3.84 (m, 1H), 3.54ꢀ3.53 (m, 2H), 3.41 (s, 3H),
3.00ꢀ2.98 (t, 2H, J = 7.8 Hz), 2.66 (d, 1H, J = 3.0 Hz), 2.21 (s, 3H), 2.11 (s, 3H); 13CꢀNMR (150 MHz, CDCl3) δ 166.4,
164.5, 157.2, 151.1, 149.9, 131.2, 129.8, 122.3, 116.1, 115.0, 98.1, 90.1, 88.8, 86.2, 82.1, 71.8, 70.0, 67.8, 62.7, 58.8, 34.3,
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