N. Šimůnková, T. Tobrman, V. Eigner, and D. Dvořák
Vol 000
2-((Trimethylsilyl)oxy)ethan-1-amine hydrochloride (3a).
White solid; yield 95%; H NMR (300 MHz, CDCl3): δ
were evaporated in vacuum and subjected to the
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chromatography on silica (EtOAc/MeOH 9:1).
N6-(2-Hydroxyethyl)adenine (1a).
Yellow solid, mp
0.15 (s, 9H, 3CH3), 3.10 (t, J = 5 Hz, 2H, CH2), 3.83 (t,
J = 5 Hz, 2H, CH2), 8.35 ppm (bs, 3H, NH+3); 13C NMR
241–246°C (Ref. [24] monohydrate 253°C); yield 97%;
1H NMR (500 MHz, DMSO-d6): δ 3.57 (m, 4H, CH2),
4.81 (s, 1H, OH), 7.44 (s, 1H, NH), 8.09 (s, 1H, H-8),
8.18 (s, 1H, H-2), 12.64 ppm (s, 1H, NH) in accordance
with Ref. [24]; 13C NMR (125 MHz, DMSO-d6): δ 42.5,
59.8, 138.7, 152.3 ppm, signals of the quaternary carbons
C4, C5, and C6 are missing owing to tautomery
commonly occurring in purine systems.
(75 MHz, CDCl3): δ ꢀ0.6, 41.6, 58.2 ppm.
3-((Trimethylsilyl)oxy)propan-1-amine hydrochloride (3b).
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White solid; yield 99%; H NMR (300 MHz, CDCl3): δ
0.09 (s, 9H, 3CH3), 1.95 (m, 2H, CH2), 3.13 (t, J = 7 Hz,
2H, CH2), 3.7 (t, J = 5 Hz, 2H, CH2), 7.89 ppm (bs, 3H,
NH+3); 13C NMR (75 MHz, CDCl3): δ ꢀ0.7, 29.7, 38.4,
60.3 ppm.
N6-(3-Hydroxypropyl)adenine (1b).
White solid, mp
4-((Trimethylsilyl)oxy)butan-1-amine hydrochloride (3c).
1
1
White solid; yield 94%; H NMR (300 MHz, CDCl3): δ
102–104°C; yield 96%; H NMR (500 MHz, DMSO-d6):
δ 1.80 (m, 2H, CH2), 3.55 (t, J = 13 Hz, 2H, OCH2),
3.64 (t, J = 13 Hz, 2H, NCH2), 7.21 (s, 1H, NH), 8.00 (s,
1H, H-8), 8.18 ppm (s, 1H, H-2); 13C NMR (125 MHz,
DMSO-d6): δ 32.1, 37.3, 58.4, 116.4, 138.6, 151.7,
153.4 ppm, signal of the quaternary carbon C4 is missing
owing to tautomery commonly occurring in purine
systems; IR (ATR): 3303, 3050, 2928, 2835, 2728, 1638,
1599, 1388, 1335, 1300, 1072 cmꢀ1; HRMS (EI): m/z
[M + H]+ calcd for C8H12N5O: 194.10419. Found:
194.10336.
0.11 (s, 9H, 3CH3), 1.64 (m, 2H, CH2), 1.85 (m, 2H,
CH2), 3.05 (m, 2H, CH2), 3.61 (t, J = 6 Hz, 2H, CH2),
8.30 ppm (bs, 3H, NH+3); 13C NMR (75 MHz, CDCl3): δ
ꢀ0.6, 24.6, 29.5, 39.8, 61.7 ppm.
5-((Trimethylsilyl)oxy)pentan-1-amine hydrochloride (3d).
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White solid; yield 83%; H NMR (300 MHz, CDCl3):
δ 0.08 (s, 9H, 3CH3), 1.43 (m, 2H, CH2), 1.54 (m,
2H, CH2), 1.78 (m, 2H, CH2), 2.98 (t, J = 8 Hz,
2H, CH2), 3.56 (t, J = 6 Hz, 2H, CH2), 7.93 ppm (bs, 3H,
NH+3).
2-Methyl-1-((trimethylsilyl)oxy)propan-2-amine hydrochloride
N6-(4-Hydroxybutyl)adenine (1c).
Light yellow solid,
(3e). White solid; yield 86%; 1H NMR (300 MHz,
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mp 186–187°C (Ref. [25] 191°C); yield 95%; H NMR
(500 MHz, CD3OD): δ 1.67 (m, 2H, CH2), 1.78 (m, 2H,
CH2), 3.63 (t, J = 6 Hz, 4H, CH2), 8.06 (s, 1H, H-8),
8.23 ppm (s, 1H, H-2); 13C NMR (125 MHz, CD3OD): δ
27.1, 30.9, 41.5, 62.6, 119.1, 140.4, 152.8, 153.8,
155.8 ppm; IR (ATR): 3260, 3211, 2941, 2857, 2788,
1619, 1598, 1316, 1247, 1070 cmꢀ1; HRMS (EI): m/z
[M + H]+ calcd for C9H14N5O: 208.11984. Found:
208.11900.
CDCl3): δ 0.14 (s, 9H, 3CH3), 1.35 (s, 6H, 2CH3),
3.49 (s, 2H, CH2), 7.51 ppm (bs, 3H, NH+3); 13C
NMR (75 MHz, CDCl3): δ ꢀ0.6, 22.8, 55.1, 68.1 ppm.
2-((Trimethylsilyl)oxy)propan-1-amine hydrochloride (3f).
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White solid; yield 99%; H NMR (300 MHz, CDCl3): δ
0.16 (s, 9H, CH3), 1.20 (d, 3H, CH3, J = 6.3 Hz), 2.80
(m, 1H, CHaHb), 2.99 (m, 1H, CHaHb), 4.13 (m, 2H,
CH2), 8.30 ppm (s, 2H, NH2); 13C NMR (75 MHz,
CDCl3): δ 0.3, 21.2, 46.3, 64.7 ppm.
N6-(5-Hydroxypentyl)adenine (1d).
Light yellow solid,
1-((Trimethylsilyl)oxy)butan-2-amine hydrochloride (3g).
mp 175–177°C; yield 84%; 1H NMR (500 MHz, CD3OD):
δ 1.51 (m, 2H, CH2), 1.61 (m, 2H, CH2), 1.73 (m, 2H,
CH2), 3.58 (m, 4H, CH2), 8.06 (s, 1H, H-8), 8.22 ppm (s,
1H, H-2); 13C NMR (125 MHz, CD3OD): δ 24.3, 30.4,
33.4, 41.7, 62.8, 119.1, 140.4, 152.9, 153.8, 155.8 ppm; IR
(ATR): 3262, 3210, 3071, 2928, 2854, 2794, 2726, 1620,
1597, 1328, 1313, 1250 cmꢀ1; HRMS (EI): m/z [M + H]+
calcd for C10H16N5O: 222.13549. Found: 222.13468.
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White solid; yield 92%; H NMR (300 MHz, CDCl3): δ
0.16 (s, 9H, CH3), 1.02 (t, 3H, CH3, J = 6.9 Hz), 1.75
(m, 1H, CHaHb), 1.86 (m, 1H, CHaHb), 3.16 (m, 1H,
CH), 3.67 (m, 1H, OCHaHb), 3.78 ppm (m, 1H,
OCHaHb); 13C NMR (75 MHz, CDCl3): δ ꢀ0.6, 10.1,
22.4, 55.0, 61.2 ppm.
N-Methyl-2-((trimethylsilyl)oxy)ethan-1-amine hydrochloride
(3h).
White solid; yield 98%; 1H NMR (300 MHz,
CDCl3): δ 0.14 (s, 9H, CH3), 2.74 (s, 3H, CH3), 3.08 (t,
2H, NCH2, J = 5.4 Hz), 3.93 ppm (t, 2H, OCH2,
J = 5.4 Hz); 13C NMR (75 MHz, CDCl3): δ ꢀ0.7, 33.2,
50.4, 57.5 ppm. Data are in accordance with [23].
General procedure for the synthesis of N6-(ω-hydroxyalkyl)
adenines 1a–i. To the mixture of 6-chloropurine (4) (1
equiv.), O-silylated aminoalcohol 3 (1.1 equiv.), K2CO3
(1.4 equiv.), and the catalyst (5 mol%) dry solvent (3 mL/
mmol) was added and the resulted mixture was stirred at
80°C for the time indicated in Table 1. After cooling to
the room temperature, the reaction was quenched with
saturated solution of NH4Cl (0.5 mL/mmol); the solvents
N6-(2-Hydroxy-1,1-dimethylethyl)adenine (1e).
Light
yellow foam, yield 95%; 1H NMR (300 MHz,
DMSO-d6): δ 1.15 (s, 6H, CH3), 3.39 (s, 2H, CH2), 6.29
(s, NH), 8.20 (s, 1H, H-8), 8.41 ppm (s, 1H, H-2); 13C
NMR (75 MHz, DMSO-d6): δ 22.8, 54.6, 66.9, 132.2,
145.4, 148.4, 154.9, 161.7 ppm; HRMS (EI): m/z
[M + H]+ calcd for C9H14N5O: 208.11929. Found:
208.11932.
N6-(1-Hydroxybutan-2-yl)adenine (1f).
yield 32%; H NMR (300 MHz, DMSO-d6): δ 0.88 (t,
3H, CH3, J = 7.5 Hz), 1.64 (m, 2H, CH2), 3.48 (m, 2H,
CH2), 4.20 (s, 1H, CH), 4.73 (s, 1H, OH), 7.06 (d, 1H,
Orange solid,
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet