aqueous potassium permanganate. 1H NMR spectra were
recorded on a Bruker Avance 300 MHz spectrometer using the
residual solvent peak as an internal reference. Chemical shifts
δ are given in parts per million (ppm). Coupling constants, J,
are given in Hz. 13C NMR spectra were recorded on the above
spectrometer or on a Bruker Aspect 3000, both operating
at 75.4 MHz. Additional PENDANT, HMBC and HMQC
experiments were performed for full assignment where neces-
sary. IR spectra were run on an FTIR Perkin-Elmer 2000
spectrophotometer as KBr pellets or as liquid films on KBr
plates. Mass spectra were either performed by the St Andrews
Analytical Services or by the EPSRC Mass Spectrometry
Service at Swansea, using electron impact (EI), chemical ionis-
ation (CI) or electrospray (ESI) techniques. Elemental analyses
were performed by the St Andrews Analytical Service within
the School of Chemistry Service.
6-Chloro-9-(tetrahydro-pyran-2-yl)-2-(tributylstannyl)-9H-
purine 9
To a stirred solution of 2,2,6,6-tetramethylpiperidine (19.5 mL,
115.5 mmol) in dry hexane (15 mL) and dry THF (30 mL) was
added dropwise at Ϫ78 ЊC n-butyllithium (48.5 mL, 2.6 M solu-
tion in hexanes, 121.3 mmol) over 30 minutes. Following stir-
ring at the same temperature for 1 hour, was added dropwise a
solution of 9-protected purine 8 (5.5 g, 23.1 mmol) in dry THF
(30 mL). After 30 minutes of stirring at Ϫ78 ЊC was added
dropwise to the dark mixture tributyltin chloride (31.3 mL,
115.5 mmol) and stirring at the same temperature was con-
tinued for 1 hour. The resulting dark solution was quenched by
dropwise addition of a saturated aqueous ammonium chloride
solution (50 mL). Following overnight warming to room tem-
perature with stirring, saturated aqueous sodium carbonate
(50 mL) was added. Extraction with ethyl acetate (2 × 50 mL)
and drying of the combined organics over magnesium sulfate
afforded after evaporation to full dryness a yellowish oil. Purifi-
cation by flash column chromatography using hexane/ethyl
acetate (4 : 1) afforded the 2-stannylated purine 9 (12.20 g,
100%) as a colourless oil; Rf 0.11 [hexane/ethyl acetate 4 : 1];
δH (300 MHz, CDCl3) 0.81 (t, 3J(1H–1H), 7.4 Hz, 9H,
6-Chloro-9H-purine monohydrate 7
To a stirred mixture of hypoxanthine 6 (7.00 g, 11.2 mmol) in
dry DMA (18 mL, 140 mmol) was added dropwise at 0 ЊC
phosphoryl oxychloride (175 mL, 1.9 mol) over a 30 minute
period. The pale green mixture was heated at reflux for 2 hours
to give a red solution. Following evaporation to dryness into a
reddish oil, icy water (200 mL) was slowly added and the green
solution was carefully neutralised to pH 9 with concentrated
ammonia. The solution was evaporated to dryness into a
yellow solid which was recrystallised twice from water to afford
6-chloropurine 7 (8.26 g, 86%) as a pale yellow crystalline solid,
decomposition at 280 ЊC (lit., mp 250 ЊC); δH (300 MHz, d6-
dmso) 3.49 (s, 2H, H2O), 8.67 (s, 1H, H8), 8.71 (s, 1H, H2);
δC (75.4 MHz, d6-dmso) 129.4 (C5), 146.1 (C8), 147.7 (C6),
151.4 (C2) 154.2 (C4); MS (CI): m/z 155 [M ϩ H]ϩ; IR (KBr):
3478s, 3428s, 3121m, 3059m, 2974m, 2808m, 2710m, 2544m,
1655w, 1607s, 1574s, 1478w, 1449m, 1427w, 1397s, 1332s,
1285w, 1239s, 1157w, 1114w, 1002w, 940m, 922w, 861s, 730m,
678w, 639s, 603m, 556m, 508m cmϪ1. Anal. Found: C, 34.80; H,
2.92; N, 32.47. Calc. for C5H3ClN4: C, 35.02; H, 2.62; N,
32.39%.
3
[CH3(CH2)3]3Sn), 1.13 (t, J(1H–1H) 7.9 Hz, 6H, [CH3(CH2)2-
CH2]3Sn), 1.27 (m, 3J(1H–1H) 7.7 Hz, 6H, [CH3CH2
3
(CH2)2]3Sn), 1.55 (m, J(1H–1H) 7.7 Hz, 9H [CH3 CH2CH2-
CH2]3Sn and THP), 1.75 (m, 2H, THP) 2.10 (m, 2H, THP), 3.72
(td, 3J(1H–1H) 3.3 & 11.8 Hz, 1H, THP H3Ј), 4.13 (dm, 3J (1H–
1H), 11.5 Hz, 1H, THP H3Ј), 5.71 (dd, 3J(1H–1H) 2.8 & 7.2 Hz,
1H, THP H1Ј), 8.15 (s, 1H, purine H8); δC (75.4 MHz, CDCl3)
9.7 (t, 1J(13C–119Sn) 165.3 Hz, [CH3(CH2)2CH2]3Sn), 12.7
([CH3(CH2)3]3Sn), 21.7 (THP C4Ј), 23.9 (THP C3Ј), 26.2 (t,
3
2J(13C–119Sn) 27.1 Hz, [CH3CH2CH2CH2]3Sn), 27.9 (t, J(13C–
119Sn) 10.5 Hz, [CH3CH2CH2CH2]3Sn), 30.8 (THP C2Ј), 67.7
(THP C5Ј), 81.5 (THP C1Ј), 129.2 (purine C5), 140.6 (purine
C8), 148.2 (purine C6), 149.1 (purine C4), 180.8 (purine C2);
MS (ESI): m/z 529 [M ϩ H]ϩ, 155 [M Ϫ THP Ϫ Sn(Bu)3]ϩ;
Found (ESI): m/z 529.1746 [M ϩ H]ϩ; C22H37ClN4OSn requires
529.1751; IR (KBr): 3110m, 2955s, 2873s, 2731m, 2669m,
2637w, 2585w, 2419w, 2217w, 2050w, 1929w, 1743w, 1651m,
1582s, 1538s, 1486s, 1464s, 1414s, 1394s, 1377s, 1342s, 1309s,
1279s, 1225s, 1210s, 1180s, 1155s, 1138s, 1087s, 1059s, 1046s,
1023s, 1005s, 945s, 935m, 911s, 877s, 857s, 844m, 823m, 788s,
769w, 747w, 694s, 650s, 590m, 545w, 509m cmϪ1. Anal. Found:
C, 50.04; H, 7.07; N, 10.62. Calc. for C22H37ClN4OSn: C, 50.04;
H, 7.34; N, 10.82%.
6-Chloro-9-(tetrahydro-pyran-2-yl)-9H-purine 8
To a stirred mixture of 6-chloropurine 7 (4.35 g, 28.2 mmol)
and p-toluenesulfonic acid (72 mg, 0.4 mmol) in dry THF
(40 mL) was added at 80 ЊC 2,3-dihydropyran (3 mL, 32.9
mmol). Reflux under a nitrogen atmosphere was continued
overnight, concentrated ammonia (2.5 mL) was added dropwise
following cooling to room temperature. After evaporation to
dryness, the yellowish oil was dissolved in ethyl acetate
(100 mL) and extracted with brine (50 mL), water (2 × 50 mL)
then dried over anhydrous sodium sulfate. The organic extracts
were concentrated in vacuo into a yellow oil that was extracted
with boiling petroleum ether 60–80 ЊC. The ether extracts were
cooled in a fridge overnight to precipitate a colourless powder
that was recrystallised from petroleum ether 60–80 ЊC to afford
6-chloro-9-THP-purine 8 (3.38 g, 68%) as colourless crystals
(needles), mp 70 ЊC (lit., 69–71 ЊC); δH (300 MHz, d6-dmso) 1.58
(m, 3H, THP), 1.74 (m, 2H, THP), 2.00 (m, 2H, THP), 2.30 (m,
1H, THP), 3.70 (m, 1H, THP H3Ј), 4.00 (dm, 3J(1H–1H)
10.8 Hz, 1H, THP H2Ј), 5.76 (dd, 3J(1H–1H) 2.3 & 11 Hz, 1H,
THP H1Ј), 8.79 (s, 1H, purine H8), 8.90 (s, 1H, purine H2);
δC (75.4 MHz, d6-dmso) 22.5 (THP C3Ј), 24.8 (THP C4Ј), 30.0
(THP C2Ј), 68.1 (THP C6Ј), 82.0 (THP C1Ј), 131.3 (purine C5),
145.9 (purine C8), 149.6 (purine C6), 151.6 (purine C4), 152.1
(purine C2); MS (EI): m/z 238 [M]ϩ, 210 [M Ϫ (CH2)2]ϩ, 155
[M Ϫ THP]ϩ; IR (KBr): 3107m, 2959m, 2938m, 2873m, 1595s,
1568s, 1491m, 1467w, 1450m, 1396m, 1337s, 1300w, 1268w,
1218s, 1180m, 1145m, 1086s, 1045s, 951s, 907m, 878w, 856m,
822w, 794w, 783w, 648m, 636m, 596m cmϪ1. Anal. Found: C,
50.32; H, 4.65; N, 23.47. Calc. for C10H11ClN4O: C, 50.63; H,
4.51; N, 23.48%.
6-Chloro-2-iodo-9-(tetrahydro-pyran-2-yl)-9H-purine 10
To a stirred solution of 2-stannylated purine 9 (12.20 g, 23.1
mmol) in dry THF (200 mL) was added iodine (9 g, 35.3 mmol)
portionwise. Stirring was continued for 24 hours under a nitro-
gen atmosphere. Following treatment with excess iodine with
saturated sodium metabisulfite, and subsequent stirring for one
hour, the solution was extracted with dichloromethane (3 ×
100 mL). The combined organics were washed with brine (100
mL), water (100 mL), dried over magnesium sulfate, then evap-
orated to full dryness into a yellowish oil. Trituration with
n-hexane (75 mL) precipitated the 2-iodopurine 10 (8.0 g, 95%)
as a pale yellow solid, mp 114 ЊC (lit., 112–113 ЊC); Rf 0.28
[hexane/ethyl acetate 1 : 1]; δH (300 MHz, CDCl3) 1.46 (m, 3H,
THP), 1.78 (m, 2H, THP), 2.01 (m, 1H, THP), 3.72 (td, 3J(1H–
3
1H) 3.6 & 11.5 Hz, 1H, THP H3Ј), 4.10 (dm, J(1H–1H) 1.8 &
11.8 Hz, 1H, THP H2Ј), 5.70 (dd, 3J(1H–1H) 2.3 & 10.5 Hz, 1H,
THP H1Ј), 8.22 (s, 1H, purine H8); δC (75.4 MHz, CDCl3) 22.4
(THP C4Ј), 24.6 (THP C3Ј), 32.0 (THP C2Ј), 68.9 (THP C5Ј),
82.3 (THP C1Ј), 116.5 (purine C5), 131.5 (purine C2), 143.0
(purine C8), 150.3 (purine C6), 151.6 (purine C4); MS (ESI):
m/z 365 [M ϩ H]ϩ, 239 [M Ϫ I]ϩ; Found (ESI): m/z 364.9665
[M ϩ H]ϩ; C10H22ClIN4O requires 364.9661; IR (KBr): 3111m,
2957m, 2684m, 1795w, 1589s, 1546s, 1485m, 1471m, 1454w,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 6 6 5 – 6 7 0
668