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0.44 mmol) were dried in vacuo for 1 h. Anhydrous N,N-
dimethylformamide (5 mL) and anhydrous triethylamine
(0.7 mL, 4.38 mmol) were added under argon. The reaction
mixture was stirred for 10 min and (Ph3P)4Pd(0) (252 mg,
0.219 mmol) was added in one portion. The reaction mixture
was stirred at room temperature with exclusion of light over-
night, concentrated in vacuo and purified by flash column
chromatography (EtOAc/toluene, 3:2, containing 1% pyri-
dine), which provided 4.16 g (87%) of 8 as a yellow foam.
(598 mg, 0.52 mmol). The reaction mixture was then stirred
at room temperature with exclusion of light overnight after
which the organic phase was washed with brine (2ꢂ
30 mL) and dried over anhydrous Na2SO4. After filtration,
the solvent was removed in vacuo and the residue purified
by flash column chromatography (hexane) to give 4 as a yel-
low solid (1.70 g, 63%). Rf 0.20 (hexane); 1H NMR
(300 MHz, CDCl3) d 8.66 (d, J¼8.5 Hz, 2H), 8.45 (s, 1H),
8.80 (d, J¼8.5 Hz, 2H), 7.64–7.49 (m, 4H), 6.60 (d,
J¼7.2 Hz, 1H), 8.66 (d, J¼7.2 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 132.7, 131.1, 128.6 (2ꢂCH), 128.4 (CH), 128.2
(CH), 126.9 (2ꢂCH), 126.7 (2ꢂCH), 125.7 (2ꢂCH),
112.5 (CH), 94.6, 94.5.
1
Rf 0.26 (EtOAc/toluene, 3:2); H NMR (300 MHz, CDCl3)
d 11.91 (s, 1H, NH-3), 8.63 (s, 1H, CH-6), 8.40 (d,
J¼8.5 Hz, 2H), 8.31 (s, 1H), 8.62 (d, J¼8.5 Hz, 2H),
7.52–7.01 (m, 13H0), 6.76 (d, J¼9.0 Hz, 1H), 6.23 (t,
0
J¼6.6 Hz, 1H, CH1 ), 5.34 (m, 1H, OH3 ), 4.28 (m, 1H,
0
0
CH3 ), 3.97 (m, 1H, CH4 ), 3.48 (s, 3H, CH3DMT), 3.46 0(s,
4.1.6. 10-(Buta-1,3-diynyl)anthracene (5). To a stirred so-
lution of 4 (100 mg, 0.38 mmol) in anhydrous tetrahydro-
furan (10 mL) was added 1.0 M nBu4NF in tetrahydrofuran
(0.95 mL, 0.95 mmol) under argon. After stirring for 24 h
the organic phase was diluted with diethyl ether (50 mL),
washed with satd aqueous NH4Cl (2ꢂ15 mL) followed by
satd aqueous NaCl (2ꢂ15 mL) and dried over anhydrous
Na2SO4. After filtration, the solvent was removed in vacuo
and the residue purified by flash column chromatography
(hexane) to give 5 (65 mg, 63%) as a yellow solid. Rf 0.23
(hexane); 1H NMR (300 MHz, CDCl3) d 8.52 (d,
J¼8.6 Hz, 2H), 8.44 (s, 1H), 8.00 (d, J¼8.4 Hz, 2H),
7.64–7.49 (m, 4H), 2.82 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 134.3, 130.9, 129.2, 128.8 (2ꢂCH), 127.3
(2ꢂCH), 126.3 (2ꢂCH), 125.9 (2ꢂCH), 84.2, 74.0 (CH),
72.7, 68.5.
0
3H, CHD3 MT), 3.27 (m, 2H, CH25 ), 2.50 (m, 1H, CH22 a),
0
2.29 (m, 1H, CH22 b); 13C NMR (75 MHz, DMSO-d6)
d 161.5 (C4), 157.8, 149.3 (C2), 144.6, 142.5 (CH-6),
135.4, 135.3, 131.4, 130.5, 129.5, 128.7, 128.5, 128.1,
127.7, 127.6, 127.5, 126.8, 126.5, 125.7, 0 125.2, 116.1,
113.0, 98.8 (C5), 0 93.2, 89.4, 85.9 (CH4 ), 85.7, 85.4
0
0
(CH1 ), 70.4 (CH3 ), 63.6 (CH25 ), 54.6 (2ꢂOCH3), 40.2
0
(CH22 ); MS (ES+) m/z: 753.0 [M+Na]+; HR-ESIMS calcd
for C46H38N2NaO7: 753.2571, found: 753.2564.
4.1.4. 50-O-(4,40-Dimethoxytrityl)-5-[10-ethynylanthra-
cenyl]-20-deoxyuridine-30-O-(2-cyanoethyl-N,N-di-
isopropyl) phosphoramidite (11). 50-O-(4,40-Dimethoxy-
trityl)-5-[10-ethynylanthracenyl]-20-deoxyuridine 8 (730 mg,
1.0 mmol) was evaporated with freshly distilled tetrahydro-
furan (2ꢂ5 mL). The resulting syrup was dissolved in
freshly distilled tetrahydrofuran (5 mL). Anhydrous N,N-
diisopropylethylamine (387 mg, 3.0 mmol) was then added
to the solution by syringe under a weak flow of argon. The
phosphitylating reagent, 2-cyanoethyl N,N-diisopropyl-
chlorophosphoramidite (295 mg, 1.3 mmol), was added
slowly via syringe and a white precipitate quickly formed.
The reaction mixture was stirred at room temperature for
2 h and diluted with dichloromethane (20 mL), then satd
aqueous KCl solution (5 mL) was added by syringe with vig-
orous stirring under argon. The organic phase was dried over
anhydrous Na2SO4 under argon for 2 h, then filtered, evapo-
rated to dryness under reduced pressure and purified by flash
chromatography (EtOAc/toluene, 1:1, containing 1% pyri-
dine). The desired phosphoramidite monomer was obtained
as a yellow solid (760 mg, 82%). Rf 0.35 (EtOAc/toluene,
1:1); 31P NMR (121 MHz, DMSO-d6) d 148.88, 148.53;
1H NMR (300 MHz, DMSO-d6) d 11.92 (s, 1H, NH-3),
8.63 (s, 1H, CH-6), 8.40 (d, J¼8.5 Hz, 1H), 8.38 (m, 2H),
8.11 (d, J¼8.4 Hz, 3H), 7.56–7.03 (m, 13H), 6.76 (d,
4.1.7. 50-O-(4,40-Dimethoxytrityl)-5-[10-(buta-1,3-diynyl)-
anthracenyl]-20-deoxyuridine (9). 50-O-(4,40-Dimethoxy-
trityl)-5-iodo-20-deoxyuridine 7 (656 mg, 1.0 mmol), 10-
(buta-1,3-diynyl)anthracene 5 (270 mg, 1.2 mmol) and CuI
(38 mg, 0.20 mmol) were dried in vacuo for 1 h. Anhydrous
N,N-dimethylformamide (5 mL) and anhydrous triethyl-
amine (0.45 mL, 3.0 mmol) were then added under argon.
The mixture was stirred for 10 min and (Ph3P)4Pd(0)
(115 mg, 0.10 mmol) was added in one portion. After stir-
ring at room temperature overnight with exclusion of light,
the reaction mixture was concentrated in vacuo and purified
by flash column chromatography (EtOAc/toluene, 3:2, con-
taining 1% pyridine) to provide 9 (588 mg, 80%) as a yellow
1
foam. Rf 0.25 (EtOAc/toluene, 3:2); H NMR (300 MHz,
CDCl3) d 11.89 (s, 1H, NH-3), 8.74 (s, 1H, CH-6), 8.33
(m, 3H), 8.18 (d, J¼7.8 Hz, 2H), 7.66–7.15 (m, 13H), 6.85
(d, J¼8.7 Hz, 2H)0, 6.87 (d, J¼8.7 Hz, 2H), 6.17 (t,
0
J¼6.6 Hz, 1H, CH1 ), 5.38 (d, J¼4.2 Hz, 1H, OH3 ), 4.39
0
0
(m, 1H, CH3 ), 4.00 (m, 1H, CH4 ), 3.66 (s, 3H,0OCHD3 MT),
0
0
J¼9.0 Hz, 4H), 6.29 (m, 1H, CH1 ), 4.50 (CH3 ), 4.10 (m,
3.65 (s, 3H, OCHD3 MT), 3.38–3.18 (m, 2H, CH52 ), 2.35 (m,
0
0
1H, CH4 ), 3.73–3.26 (m, 12H, 2ꢂOCH3, OCH2CH2CN,
2H, CH22 ); 13C NMR (75 MHz, DMSO-d6) d 161.4 (C4),
158.0, 149.1 (C2), 145.6 (CH-6), 144.6, 135.5, 135.2,
133.0, 130.5, 129.6, 129.5, 129.3, 129.1, 128.7, 128.1,
0
0
CH52 ), 2.58–2.27 (m, 4H, CH22 , ((CH3)2CH)2N), 1.13–0.97
(m, 12H, ((CH3)2CH)2N); MS (ES+) m/z: 931.4 [M+Na]+;
HR-ESIMS calcd for C55H55N4NaO8P: 953.3650, found:
953.3646.
128.1, 127.8, 127.5, 126.6, 126.1, 125.3, 0 125.2, 113.9,
0
113.1, 97.0 (C5), 86.0 (CH4 ), 85.9 (CH1 ), 85.4, 84.5,
0
0
78.2, 78.1, 76.5, 70.1 (CH3 ), 63.5 (CH25 ), 54.9 (2ꢂOCH3),
0
4.1.5. 10-((Z)-4-Chlorobut-3-en-1-ynyl)anthracene (4).
10-Ethynylanthracene 3 (2.10 g, 10.4 mmol) was dissolved
in anhydrous toluene (100 mL). cis-1,2-Dichloroethylene
(2.04 g, 21 mmol) and anhydrous n-butylamine (52 mmol,
5.2 mL) were introduced to the solution under argon
followed by CuI (200 mg, 1.04 mmol) and (Ph3P)4Pd(0)
40.2 (CH22 ); MS (ES+) m/z: 777.2 [M+Na]+; HR-ESIMS
calcd for C48H38N2NaO7: 777.2571, found: 777.2559.
4.1.8. 50-O-(4,40-Dimethoxytrityl)-5-[10-(buta-1,3-
diynyl)anthracenyl]-20-deoxyuridine-30-O-(2-cya-
noethyl-N,N-diisopropyl) phosphoramidite (12). 50-O-