Beilstein J. Org. Chem. 2016, 12, 2556–2562.
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26.76, 128.08, 128.52, 128.65, 128.69, 128.77 (C(benzoyl)), DMSO-d6) δ 0.89–0.96 (q, 6H, NCHN(CH2CH2CH2CH3)2),
29.16, 129.22, 129.29, 129.39 (C(benzoyl)), 133.57, 133.86, 1.28–1.37 (sextet, J = 6.8 Hz, 4H, NCHN(CH2CH2CH2CH3)2),
33.95 (C(benzoyl)), 137.12, 139.98 (C-(8)), 140.98 (C-(2)), 1.53–1.64 (quintet, J = 7.8 Hz, 4H, NCHN(CH2CH2-
52.55, 164.31, 164.70, 165.45 ppm; HRMS [M + H+]: calcd CH2CH3)2), 3.22–3.27 (m, 2H, H-C(5’)), 3.33–3.40 (t, J = 7.3
for C32H26N4O7+, 579.1880; found, 579.1852.
Hz, 4H, NCHN(CH2CH2CH2CH3)2), 3.72 (s, 6H, 2 × OCH3),
.09–4.10 (d, J = 4.1 Hz, 1H, H-C(4’)), 4.19–4.21 (m, 1H,
-Deazaadenosine (5). Compound 4 (1.231 g, 2.13 mmol) was H-C(3’)), 4.45–4.46 (m, 1H, H-C(2’)), 5.25–5.27 (m, 1H,
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dissolved in a solution of 33% methylamine in ethanol (10 mL) OH-C(3’)), 5.60–5.62 (m, 1H, OH-C(2’)), 5.86–5.87 (d, J = 5.2
and 40% methylamine in water (10 mL) and stirred for 18 hours Hz, 1H, H-C(1’)), 6.81–6.84 (d, J = 6.8 Hz, 4H, H(ar)-DMTr),
at room temperature. All volatiles were evaporated and the 7.20–7.29 (m, 8H, H(ar)-DMTr, H-C(2)), 7.34–7.36 (d, J = 7.4
residue was dried in high vacuum. The crude product was puri- Hz, 2H, H(ar)-DMTr), 7.78–7.80 (d, J = 5.6 Hz, 1H, H-C(3)),
fied by dissolving the byproduct (N-methylbenzamide) in 8.24 (s, 1H, NCHN(CH2CH2CH2CH3)2), 8.64 (s, 1H, H-C(8))
chloroform and subsequent collection of the precipitate by ppm; 13C NMR (75 MHz, DMSO-d6) δ 13.61, 13.82
centrifugation (3000 rpm, rt, 1 min). Yield: 537.1 mg (95%) of (NCHN(CH2CH2CH2CH3)2), 19.21, 19.73 (NCHN(CH2CH2-
compound 5 as beige solid. TLC (30% methanol in dichloro- CH2CH3)2), 28.78, 30.74 (NCHN(CH2CH2CH2CH3)2), 44.06
methane): Rf = 0.23; 1H NMR (300 MHz, DMSO-d6) δ (C-(5')), 50.46, 52.07 (NCHN(CH2CH2CH2CH3)2), 55.01 (2 ×
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.57–3.68 (q, J = 10.1 Hz, 2H, H-C(5’)), 3.94–3.96 (d, J = 3.3 OCH3 (DMTr)), 63.57; 70.11 (C-(3’)), 73.40 (C-2’)), 83.38
Hz, 1H, H-C(4’)), 4.08–4.10 (d, J = 3.1 Hz, H-C(3’)), 4.30–4.32 (C-4’)), 85.66, 89.00 (C-(1’)), 101.66 (C-(3)), 112.88, 113.19
d, J = 5.5 Hz, 1H, H-C(2’)), 5.06–5.09 (t, J = 6.5 Hz, 1H, (C(ar)), 126.68, 127.71, 127.83, 129.71, 133.24 (C-(ar)),
OH-C(5’)), 5.19–5.20 (d, J = 4.0 Hz, 1H, OH-C(3’)), 5.44–5.46 135.34, 135.39, 138.92, 140.22 (C-(2)), 140.83 (NCHN(CH2-
d, J = 6.2 Hz, 1H, OH-C(2’)), 5.74–5.76 (d, J = 6.2 Hz, 1H, CH2CH2CH3)2), 144.73, 155.05, 155.88, 158.08 (C-(8)) ppm;
(
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H-C(1’)), 6.17 (s, br, 2H, NH2), 6.90–6.92 (d, J = 5.8 Hz, 1H, HRMS [M + H+]: calcd for C41H49N5O6+, 708.3761; found,
H-C(3)), 7.65–7.67 (d, J = 5.8 Hz, 1H, H-C(2)), 8.29 (s, 1H, 708.3766.
H-C(8)) ppm; 13C NMR (75 MHz, DMSO-d6) δ 61.22 (C-(5’)),
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0.08 (C-(3’)), 73.86 (C-(2’)), 85.53 (C-(4’)), 88.66 (C-(1’)), N6-[(Dibutylamino)methylene]-5’-O-(4,4’-dimethoxytrityl)-
7.37 (C-(3)), 126.91, 137.58, 139.95 (C-(8)), 140.45 (C-(2)), 2’-O-triisopropylsilyl-3-deazaadenosine (7). Compound 6
52.36 ppm; HRMS [M + H+]: calcd for C11H14N4O4+, (458 mg, 647 µmol) was weighed into a 25 mL Schlenk flask,
67.1093; found, 267.1074.
dried in high vacuum for one hour, and dissolved in dry pyri-
dine (3 mL) under argon atmosphere. Then, AgNO3 (440 mg,
N6-[(Dibutylamino)methylene]-5’-O-(4,4’-dimethoxytrityl)- 2.59 mmol) was added. The reaction solution was stirred in the
-deazaadenosine (6). Compound 5 (199 mg, 747 µmol) was dark for 15 minutes, resulting in a clear solution, after which tri-
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weighed into a 25 mL two-necked flask and dried in high isopropylsilyl chloride (0.55 mL, 2.59 mmol) was added. The
vacuum for 1 hour. Under an argon atmosphere dry pyridine reaction was allowed to proceed for 18 hours at room tempera-
(
5 mL) and N,N-dibutylformamide dimethyl acetal (0.40 mL, ture. The resulting suspension was filtered through celite and
.74 mmol) were added and stirred for 1.5 h at room tempera- partitioned between dichloromethane and 5% aqueous sodium
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ture. Afterwards, all volatiles were evaporated, the residue dried bicarbonate solution (10 mL each). The organic layer was
in high vacuum and redissolved in dry pyridine (5 mL). washed twice with 5% aqueous sodium bicarbonate solution
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-(Dimethylamino)pyridine (28.4 mg, 233 µmol) and (2 × 10 mL), dried over Na2SO4 and evaporated. The regio-
,4’-dimethoxytrityl chloride (686 mg, 2.03 mmol) were isomers were separated by flash chromatography (toluene/ethyl
added and the reaction was allowed to proceed for 16 hours. acetate/methanol = 12.5:11.5:1, size: 23.0 × 1.5 cm, 17 g silica
The reaction was quenched with methanol (1 mL) and all vola- gel). Yield: 146.2 mg (26%) of compound 7 as white foam.
tiles were evaporated, followed by coevaporation with toluene TLC: (10% methanol in dichloromethane): Rf = 0.47; 1H NMR
(
2 × 10 mL). The residue was partitioned between dichloro- (300 MHz, DMSO-d6) δ 0.77–0.79 (m, 6H, NCHN(CH2CH2-
methane (10 mL) and 5% aqueous citric acid solution (7 mL). CH2CH3)2), 0.89–0.93 (m, 18H, Si(CH(CH3)3)3), 1.23–1.35
The organic layer was separated, washed with water and satu- (sextet, J = 6.9 Hz, 4H, NCHN(CH2CH2CH2CH3)2), 1.50–1.61
rated sodium bicarbonate solution (10 mL each), dried over (quintet, J = 8.0 Hz, 4H, NCHN(CH2CH2CH2CH3)2),
Na2SO4 and evaporated. The crude product was purified by 3 . 2 4 – 3 . 3 3 ( m , 7 H , N C H N ( C H 2 C H 2 C H 2 C H 3 ) 2 ,
flash chromatography (1% methanol in dichloromethane + 1.5% Si(CH(CH3)3)3), 3.49–3.54 (t, J = 7.3 Hz, 2H, H-C(5’)), 3.70 (s,
triethylamine, size: 18.0 × 2.0 cm, 21 g silica gel). Yield: 6H, 2 × OCH3), 4.10–4.13 (m, 1H, H-C(4’)), 4.19–4.24 (m, 1H,
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12 mg (40%) of compound 6 as white foam. TLC (10% H-C(3’)), 4.67–4.71 (m, 1H, H-C(2’)), 5.20–5.22 (m, 1H,
methanol in dichloromethane): Rf = 0.32; 1H NMR (300 MHz, OH-C(3’)), 5.89–5.91 (d, J = 6.1 Hz, 1H, H-C(1’)), 6.82–6.84
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