The 't-amino effect' of ortho-nitroso amines. Synthesis of 2,6-diaminoadenine derivatives from 6-(Dialkylamino)-5-nitrosopyrimidines

Article abstract of DOI:10.1002/hlca.201100098

The 't-amino effect' of amino-nitroso compounds was documented by preparing the (dialkylamino)-nitroso pyrimidines 4-18, and cyclising them under thermal conditions in high yields to the purine derivatives 19-32. The reactivity of the amino-nitroso-pyrimi

Full text of DOI:10.1002/hlca.201100098

Helvetica Chimica Acta – Vol. 94 (2011)
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The ꢀt-Amino Effectꢁ of ortho-Nitroso Amines. Synthesis of 2,6-
Diaminoadenine Derivatives from 6-(Dialkylamino)-5-nitrosopyrimidines
by Maria del Carmen Ruiz Ruiz and Andrea Vasella*
Laboratorium fꢀr Organische Chemie, ETH Zꢀrich, Wolfgang-Pauli-Strasse 10, CH-8093 Zꢀrich
(e-mail: vasella@org.chem.ethz.ch)
The ꢁt-amino effectꢂ of amino-nitroso compounds was documented by preparing the (dialkylamino)-
nitroso pyrimidines 4 – 18, and cyclising them under thermal conditions in high yields to the purine
derivatives 19 – 32. The reactivity of the amino-nitroso-pyrimidines, particularly of 17 derived from
diethyl iminodiacetate, and of 19, derived from 1-phenylimidazolidine, correlates with the stability of the
intermediate azomethine ylide. Thermolysis of the amino-nitroso-pyrimidines 34 – 37, possessing
dialkylamino substituents at C(4) and C(6), proceeded by protiodenitrosation, leading to 38 – 41.
Introduction. – The thermal cyclisation of N,N-dialkylanilines possessing at least
one N-methylene group and substituted in the ortho-position by a p-acceptor
substituent, usually termed the ꢁt-amino effectꢂ1), has been known for a long time2),
and was periodically reviewed [6 – 9]. A large number of N,N-dialkylanilines possessing
an ortho p-acceptor substituent undergo the transformation. Among the most
important ortho-substituents are the nitro, azo, imino, sulfimino, thionitroso, carbonyl,
thiocarbonyl, and acceptor-substituted alkenyl groups. The cyclisation of ortho-nitroso
anilines according to the t-amino effect has, however, to the best of our knowledge,
never been unambiguously documented, although the intermediate formation of such
nitroso derivatives in the course of the cyclisation of ortho-(N,N-dialkyl)(amino)ani-
lines under oxidative conditions, or the cyclisation of ortho-(N,N-dialkyl)(nitro)ani-
lines under reducing conditions was postulated, as discussed by Meth-Cohn and
Suschitzky (see [7] and refs. cit. therein).
6-Amino-5-nitrosopyrimidines substituted at C(2) and C(4) are readily available,
established intermediates in the synthesis of purine and pteridine derivatives [10][11].
We have developed new methods for the transformation of 6-(acylamino)-5-nitroso-
pyrimidines into guanidines [12], pteridinones [13], pyrimido-diazepines, and diaze-
pino-purines [14]. The thermal cyclisation of 6-(dialkylamino)-5-nitrosopyrimidines
should provide unambiguous evidence for the t-amino effect of ortho-N,N-dialkyl-
nitrosoanilines, and provide a ready access to purines and purine-derived ring systems
that are of interest in view of the biological properties of many purine
1
)
The unsatisfactory designation of a reaction by the term ꢁeffectꢂ (cf. [1]) has led to the suggestion of
replacing the expression by ꢁa-cyclisation of tertiary aminesꢂ [2][3] and ꢁT-reactionꢂ [4].
The first reaction to be described by Meth-Cohn and Suschitzky as ꢁt-amino effectꢂ was reported by
Pinnow [5].
2
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ꢃ 2011 Verlag Helvetica Chimica Acta AG, Zꢀrich

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derivatives3). We expected the thermal cyclisation of 6-(dialkylamino)-5-nitrosopyr-
imidines to follow the established reaction mechanism for the t-amino effect, as shown
in Scheme 1 [16][17].
Scheme 1
We assumed that formation of azomethine ylides (C in Scheme 1) is rate-
determining, although the elimination of H2O from the cyclisation product D is
disfavoured for stereoelectronic reasons. The reactivity of the amino-nitroso-pyrimi-
dines should then reflect the influence of the nature of the substituents on the relative
stability of the azomethine ylides. We intended to evaluate the validity of this
assumption, and to explore the scope of the expected cyclisation by examining the
thermal cyclisation of open-chain and cyclic (dialkylamino)-nitroso-pyrimidines,
varying the steric and electronic properties of the dialkylamino group.
Results and Discussion. – Scouting experiments to prepare the required amino-
nitroso-pyrimidines by nitrosating 6-chloropyrimidine-2,4-diamine (1) [18]
(Scheme 2), followed by treatment of the poorly stable product with secondary
amines, resulted in no more than ca. 30% of the desired amino-nitroso-pyrimidines4).
For this reason, we turned towards 6-(phenylsulfanyl)pyrimidine-2,4-diamine (2)
[19] to prepare the desired amino-nitroso-pyrimidines 4 – 18 (Schemes 2 – 4). Both the
nitrosation of alkyl- and arylthio analogues and the subsequent substitution of the
alkyl- or arylsulfanyl group by nitrogen nucleophiles are well known [20 – 22].
Replacement of the 6-Cl substituent 1 with a PhS group by improving a known
procedure [19] afforded 2 in 92% yield. Nitrosation of 2 provided 3 in a yield of 85%.
3
)
Consideration of the biological properties of similar ring systems has led Ojea et al. [15] to use the t-
amino effect of 6-(dialkylamino)-5-(dicyanoethenyl)pyrimidines for the synthesis of fused
pyrido[2,3-d]pyrimidines.
We thank Fangli Zhang for these experiments and for the first evidence that thermolysis of 2,4-
diamino-5-nitroso-6-(pyrrolidin-1-yl)pyrimidines leads to the desired purine derivatives.
4
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We first examined the synthesis and cyclisation of the (dimethylamino)- and
(diethylamino)-nitroso pyrimidines 4 and 5, and of the unsymmetrically substituted
analogues 6 – 9 (Scheme 2).
Scheme 2
a) NaOH, MeOH/H2O, PhOH, 708; 92%. b) NaNO2, AcOH/H2O, 508; 85%. c) Secondary amine, EtOH,
D; 72 – 95%. d) Ph2O, D; 88 – 97%.
Treatment of 3 with 2 equiv. of each one of the selected acyclic secondary amines
provided the desired amino-nitroso-pyrimidines 4 – 9 in yields between 68 and 87%.
The substitution was conveniently followed by observing the colour change from purple
to red-pink. The amino-nitroso-pyrimidines 10 – 13, derived from cyclic amines, and
14 – 16, derived from less strongly basic cyclic amines (Scheme 3) were prepared in the
same way, and in similar yields. Only 17 (45%), derived from diethyl iminodiacetate,
and 18 (32%), derived from 1-phenylimidazolidine [23], were obtained in lower yields.
The IR spectra of all amino-nitroso-pyrimidines show the typical NO band between
1500 and 1600 cmꢀ1. A H-bond from C(4)NH2 to the NO group is evidenced by the
significant chemical-shift difference between the two C(4)NꢀH, one resonating at 10.70

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Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 3
a) Ph2O, 2108; 85 – 96%.
and the other at 7.60 ppm, and the C(2)NH2 group resonating between 7.04 and
7.08 ppm.
Heating the 6-(dimethylamino)-pyrimidine 4 and the diethylamino analogue 5 in
Ph2O at 200 to 2108 induced a rapid change of colour from reddish over green-brown to
deep-brown and blackish. Liquid chromatography/mass spectrometry (LC/MS) of
samples recorded before heating, and within 2 and 5 min from the beginning of heating
exhibited two new peaks, one with the same mass as the starting material, and one with
the mass expected for the final product that increased as the reaction proceeded, until it
became the only peak, at which time heating was discontinued. The product was
isolated and purified by column chromatography to provide the purines 19 (84%) and
20 (87%), respectively. The 6-(diethylamino)-pyrimidine 5 reacted slightly more
rapidly than the 6-(dimethylamino) analogue 4, reflecting the relative stability of the
more highly substituted intermediate azomethine ylide and of the transition state
leading to it. The regioselectivity of the cyclisation of the (ethyl)(methyl)amino
derivative 6 and of the (butyl)(methyl)amino derivative 7 that yielded 95% exclusively
of the purines 21 and 22, respectively, is in keeping with this interpretation. Similarly,

Helvetica Chimica Acta – Vol. 94 (2011)
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cyclization of 6-[(benzyl)(methyl)amino]-pyrimidine 8 gave exclusively the 8-phenyl-
purine 23 in 88% yield.
Cyclisation of the azomethine ylide derived from 9 should lead to an N-hydroxy
dihydropurine that cannot aromatize by simple dehydration; we expected the
migration of a Me group. However, the starting material reacted much more slowly
than 4 – 8, forming a black, complex product mixture that was not analyzed.
The amino-nitroso-pyrimidines 10 – 13, derived from cyclic amines, reacted very
similarly to each other, although more slowly than 4 – 8, derived from open-chain
amines, to provide the cyclisation products 24 – 27, all in high yields (see the Table).
Table. Starting Amino-nitroso-pyrimidine, Temperature and Duration of the Thermal Cyclisation,
Product, and Yield
Starting material
Product
T [8]
Duration [min]
Yield [%]
4
5
6
7
8
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
185
185
190
190
175
210
210
210
210
210
210
210
210
185
10
5
97
95
95
94
88
97
95
95
95
89
92
85
96
96
35
30
15
90
40
30
20
50
35
90
3
10
The trend to a diminished reactivity was most clearly visible for the pyrrolidin-1-yl
derivative 10. Its cyclisation required ca. 90 min at 2108, whereas the 6-(dimethyl-
amino)-pyrimidine reacted within 10 min at 1858. The piperidin-1-yl derivative 11
required less time for cyclization than 10. Still milder conditions led to the cyclisation of
the azepan-1-yl derivative 12 to 26 and, not surprisingly, particularly of the
tetrahydroisoquinolin-2-yl derivative 13 to 27. It reacted more rapidly than 11, but
still more slowly than the open-chain amino derivatives, indicating that the stability of
the azomethine ylide is not the only factor determining the reactivity of these amino-
nitroso-pyrimidines. The resulting purines were obtained in high yields, but proved
poorly soluble, even in DMSO.
The azepanyl and the isoquinolinyl derivatives 26 and 27, respectively, crystallized
from DMSO, and their structures were established by X-ray analysis (Figs. 1 and 2)5).
5
)
The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as
deposition No. CCDC-801183 for 26 and CCDC-801184 for 27. Copies of the data can be obtained
free of charge via http://www.ccdc.cam.ac.uk/data_request/cif (or from the Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge CB2 1EZ (fax: þ 441223336033; e-mail:
deposit@ccdc.cam.ac.uk)).

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Helvetica Chimica Acta – Vol. 94 (2011)
Fig. 1. Crystal structure of 7,8,9,10-tetrahydro-6H-azepino[1,2-e]purine-2,4-diamine (26 · DMSO)
The amino-nitroso-pyrimidines 14 – 16 (Scheme 3) were prepared to examine the
effect of the s-acceptor substituents that are expected to disfavour the hydride shift.
The effects of the p-acceptor and p-donor properties of the 6-amino substituents of 17
and 18, respectively, on the reactivity of the amino-nitroso-pyrimidines were of interest,
as both substituents should stabilize the assumed intermediate azomethine ylide, while
hydride migration from 17 was expected to be disfavoured. We also expected a
favourable effect of the substituents on the solubility of the resulting purine derivatives.
The amino-nitroso-pyrimidines 14 and 15 provided the cyclisation products 28 and
29, respectively, under similar conditions as the piperidine derivative 11 gave 25, while
the morpholine derivative 16 required clearly harsher reaction conditions to yield 30
(Table). Cyclisation of the iminodiacetate 17 to 31 (96%) and of the imidazolidinyl
derivative 18 to 32 (96%) proceeded at a lower temperature (1858 for 10 min) and
clearly more rapidly than cyclization of 14 – 16, in keeping with the intermediate
formation of an azomethine ylide. The cyclization under mild conditions of a glycine-
substituted pyrimidine-carbaldehyde via an azomethine ylide was already reported
[16], while the cyclization of N,N-acetals appears to be new.
Unfortunately, the effect of the nature of the amino group of the pyrimidines 14 – 18
on the solubility of the products 28 – 32 was rather small, all resulting purines proving
poorly soluble at neutral pH, even in DMSO.
The rather high temperature required for the cyclization may result from the donor
properties of the NH2 groups at C(2) and C(4), reducing the electrophilic properties of
the NO group and from the C(4)NH ··· ONC(5) H-bond, orienting the NO group in an
unfavourable direction. To explore the effect of this H-bond, we wished to replace the
NH2 group at C(4) by a MeO or by a dialkylamino group, treating 4,6-dimethoxy-5-
nitrosopyrimidin-2-amine6) (33) [24] with a selection of cyclic secondary amines
(Scheme 4).
6
)
We thank Lonza AG, Visp, for a generous gift of 4,6-dimethoxypyrimidin-2-amine.

Helvetica Chimica Acta – Vol. 94 (2011)
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Fig. 2. Crystal structure of 5,6-dihydropurino[8,9-a]isoquinoline-9,11-diamine (27 · 1.5 H2O · 0.5 DMSO)

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Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 4
a) Pyrrolidine, EtOH, r.t.; 88%. b) Piperidine, EtOH, r.t.; 93%. c) Morpholine, EtOH, r.t.; 80%. d)
Ethyl isonipecotate (¼ethyl piperidine-4-carboxylate), EtOH, r.t.; 85%. e) Ph2O, 2108.
However, 33 reacted with either 1 or 2 equiv. of pyrrolidine, piperidine, morpholine,
or ethyl piperidine-4-carboxylate (¼ethyl isonipecotate) under a range of reaction
conditions to consistently provide the disubstitution products 34 – 37, respectively [25],
although the reaction of the bis(benzyloxy) analogue with primary amines led to
monosubstituted products [26], conceivably on account of the intramolecular H-bond
between the first introduced C(4)NHR and the NO group.
Unexpectedly, heating the amino-nitroso-pyrimidines 34 – 37 in Ph2O under the
same reaction conditions as described before led exclusively to the products of
denitrosation, 38 – 41 (Scheme 4). To confirm the structure of the denitrosation
products that are known compounds [26], with the exception of 41, we synthesised an
authentic sample of the dimorpholino-pyrimidine 40 [27] from commercial 4,6-
dichloropyrimidin-2-amine.
We assume that the steric interaction with the ortho amino groups forces the NO
group out of the plane of the pyrimidine ring, so that, at the high temperature,
protiodenitrosation takes place, with the rather acidic 2-NH2 group acting as
protonating agent7), suggesting a significant role of the H-bond from the neighbouring
amino group in stabilizing the nitroso-pyrimidines.
We thank Dr. B. Bernet for double-checking the manuscript, Dr. T. Steinlin and Dr. F.-L. Zhang for
useful discussions, and Syngenta AG, Basel, for generous support.
7
)
We have not yet explored the effect of removing the NH2 substituents at C(2).

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Experimental Part
General: See [28].
6-(Phenylsulfanyl)pyrimidine-2,4-diamine (2) [19]. A soln. of 6-chloropyrimidine-2,4-diamine [18]
(50 g, 0.36 mol) in MeOH/H2O 3 :2 (1.5 l) was treated with NaOH (18.14 g, 0.45 mol) at r.t. PhSH
(53.5 ml, 0.52 mmol) was added dropwise. The soln. was stirred for 24 h at 1008, cooled to r.t., and
evaporated. The residue was crystallized from MeOH/H2O to afford 2 (69.4 g, 92%). White needles. A
sample for analysis was obtained by sublimation at 1358 and < 10ꢀ3 bar. Rf (CH2Cl2/MeOH 9 :1) 0.42.
M.p. 1588 ([19]: 156 – 1578). IR (ATR): 3415w, 3388m, 3170m, 3070w, 2185w, 1620s, 1541s, 1482s, 1443m,
1434m, 1364s, 1272m, 1164w, 1148m, 1091w, 1072w, 1022w, 972w, 921w, 894m, 791m. 1H-NMR (300 MHz,
(D6)DMSO): 7.59 – 7.47 (m, 5 arom. H); 6.21 (s, NH2); 6.00 (s, NH2); 5.11 (s, HꢀC(5)). 13C-NMR
(75 MHz, (D6)DMSO): 168.75 (s, C(2)); 164.16 (s, C(6)); 162.55 (s, C(4)); 135.39 (2d); 129.76 (2d);
129.50 (2d); 129.25 (s); 89.44 (d, C(5)). HR-MALDI-MS: 219.0696 (100, [M þ H]þ, C10H11N4Sþ; calc.
219.0704).
5-Nitroso-6-(phenylsulfanyl)pyrimidine-2,4-diamine (3). A soln. of 2 (2 g, 9.16 mmol) in H2O/
AcOH 8 :2 (50 ml) was treated with NaNO2 (758 mg, 11 mmol), stirred overnight at 508, and cooled to
08. The purple precipitate was filtered off and recrystallized in PrOH to afford 3 (1.92 g, 85%). Rf
(CH2Cl2/MeOH 10 :1) 0.50. M.p. 1908. IR (ATR): 3478w, 3309m, 3269m, 3119m, 3071s, 1661m, 1626s,
1
1536s, 1495s, 1474s, 1458s, 1437s, 1375s, 1331s, 1242s, 1141s, 1065m, 999s, 914s, 806m, 787m. H-NMR
(300 MHz, (D6)DMSO): 9.68 (br. d, J ¼ 3.0, NH); 8.16 (br. d, J ¼ 3.0, NH); 7.84 (br. s, NH); 7.67 – 7.63
(m, 2 arom. H); 7.59 (br. s, NH); 7.51 – 7.40 (m, 3 arom. H). 13C-NMR (75 MHz, (D6)DMSO): 181.00 (s,
C(6)); 161.01 (s, C(2)); 149.03 (s, C(4)); 144.87 (s, C(5)); 135.64 (2d); 129.27 (2d); 129.09 (2d); 127.94 (s).
HR-MALDI-MS: 248.0601 (72, [M þ H]þ, C10H10N5OSþ; calc. 248.0606), 217.0548 (100, [M ꢀ NO]þ,
C10H9N4Sþ; calc. 217.0548).
General Procedure for the Preparation of the Amines 4 – 18 (GP 1). A suspension of 3 (1 equiv.) in
EtOH or BuOH (for 9 and 16 – 18) (5 ml) was treated with the suitable secondary amine (2 equiv.) and
stirred for periods and at temps. indicated. The coloured precipitates were filtered off and dried under
vacuum.
N4,N4-Dimethyl-5-nitrosopyrimidine-2,4,6-triamine (4) [21][22]. Prepared according to GP 1 from 3
(500 mg, 2.02 mmol) and Me2NH (205 ml, 4.04 mmol) at 608 for 60 min. Yield: 320 mg (87%). Dark-pink
powder. Rf (CH2Cl2/MeOH 9 :1) 0.56. M.p. 2598 [21][22]: 258 – 2598). IR (ATR): 3107s, 1670m, 1631m,
1553s, 1479s, 1403s, 1347s, 1323s, 1227s, 1155s, 1095s, 1042s, 1000m, 880m, 835m, 787s. 1H-NMR
(300 MHz, (D6)DMSO): 10.65, 7.65 (2 br. s, H2NꢀC(6)); 7.08 (br. s, H2NꢀC(2)); 3.33 (s, NMe2).
13C-NMR (75 MHz, (D6)DMSO): 162.81, 161.96 (2s, C(2), C(4)); 151.51 (s, C(6)); 141.15 (s, C(5)); 41.86
(q, NMe2). HR-MALDI-MS: 183.0975 (100, [M þ H]þ, C6H11N6Oþ; calc. 183.0994).
N4,N4-Diethyl-5-nitrosopyrimidine-2,4,6-triamine (5). Prepared similarly to 4 according to GP 1
from 3 (500 mg, 2.02 mmol) and Et2NH (416 ml, 4.04 mmol). Yield: 358 mg (84%). Dark-pink powder. Rf
(CH2Cl2/MeOH 9 :1) 0.37. M.p. 2158. IR (ATR): 3335w, 3272w, 3125s, 1621m, 1538s, 1482s, 1457s, 1439m,
1
1428w, 1377w, 1364w, 1313s, 1244s, 1196s, 1157s, 1111s, 1073s, 1050s, 1010s, 813w, 789s, 752m. H-NMR
(300 MHz, (D6)DMSO): 10.78, 7.63 (2 br. s, H2NꢀC(6)); 7.04 (br. s, H2NꢀC(2)); 3.74 (q, J ¼ 6.7,
N(CH2Me)2); 1.19 (t, J ¼ 6.9, N(CH2Me)2). 13C-NMR (75 MHz, (D6)DMSO): 162.10 (s, C(2)); 161.37 (s,
C(4)); 151.58 (s, C(6)); 104.90 (s, C(5)); 45.36 (t, N(CH2Me)2); 13.42 (q, N(CH2Me)2). HR-MALDI-MS:
211.298 (100, [M þ H]þ, C8H15N6Oþ; calc. 211.1307), 193.1201 (49, [M ꢀ OH]þ, C8H13Nþ6 ; calc. 193.1202).
N4-Ethyl-N4-methyl-5-nitrosopyrimidine-2,4,6-triamine (6). Prepared according to GP 1 from 3
(500 mg, 2.02 mmol) and ethyl(methyl)amine (351 ml, 4.04 mmol) at 608 for 75 min. Yield: 314 mg
(79%). Dark-pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.38. M.p. 2358. IR (ATR): 3278m, 3096s, 1671m,
1633m, 1539s, 1490s, 1458w, 1407m, 1361m, 1340s, 1317s, 1222s, 1199s, 1156s, 1099m, 1068m, 1049s, 1033m,
1
1003s, 853w, 823m, 787s, 752w. H-NMR (300 MHz, (D6)DMSO): 10.72, 7.64 (2 br. s, H2NꢀC(6)); 7.07
(br. s, H2NꢀC(2)); 3.81 (q, J ¼ 7.1, NCH2Me); 3.31 (s, NMe); 1.18 (t, NCH2Me). 13C-NMR (75 MHz,
(D6)DMSO): 162.13, 162.04 (2s, C(2), C(4)); 151.55 (s, C(6)); 141.09 (s, C(5)); 47.77 (t, NCH2Me); 43.13
(q, NMe); 12.94 (q, NCH2Me). HR-MALDI-MS: 197.1145 (100, [M þ H]þ, C7H13N6Oþ; calc. 197.1151),
179.1040 (54, [M ꢀ OH]þ, C7H11N6þ ; calc. 179.1040).

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N4-Butyl-N4-methyl-5-nitrosopyrimidine-2,4,6-triamine (7). Prepared similarly to 6 according to
GP 1 from 3 (500 mg, 2.02 mmol) and butyl(methyl)amine (482 ml, 4.04 mmol). Yield: 355 mg (78%).
Pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.59. M.p. 2048. IR (ATR): 3499s, 3140s, 2951s, 2928m, 2869w,
1599m, 1543s, 1484s, 1461s, 1407m, 1344s, 1311s, 1266w, 1226s, 1173m, 1144s, 1102s, 1058w, 1033w, 990s,
878w, 849m, 789s. 1H-NMR (300 MHz, (D6)DMSO): 10.71, 7.63 (2 br. s, H2NꢀC(6)); 7.05 (br. s,
H2NꢀC(2)); 3.78 (t, J ¼ 7.5, NCH2); 3.33 (s, NMe); 1.02 (quint., J ¼ 6.9, NCH2CH2); 1.27 (sext., J ¼ 7.3,
CH2Me); 0.89 (t, J ¼ 7.2, CH2Me). 13C-NMR (75 MHz, (D6)DMSO): 161.99, 161.95 (2s, C(2), C(4));
151.63 (s, C(6)); 150.43 (s, C(5)); 52.60 (t, NCH2); 39.82 (q, NMe); 29.38 (t, NCH2CH2); 19.40 (t,
CH2Me); 13.75 (q, CH2Me). HR-MALDI-MS: 225.1458 (100, [M þ H]þ, C9H17N6Oþ; calc. 225.1464),
207.1352 (88, [M ꢀ OH]þ, C9H15N6þ ; calc. 207.1358), 194.1400 (74, [M ꢀ NO]þ, C9H16Nþ5 ; calc. 194.1406).
Anal. calc. for C9H16N6O (224.27): C 48.20, H 7.19, N 37.47; found: C 48.09, H 7.14, N 37.29.
N4-Benzyl-N4-methyl-5-nitrosopyrimidine-2,4,6-triamine (8). Prepared according to GP 1 from 3
(250 mg, 1.01 mmol) and benzyl(methyl)amine (260 ml, 2.02 mmol). Yield: 193 mg (74%). Pink powder.
Rf (CH2Cl2/MeOH 9 :1) 0.44. M.p. 2278. IR (ATR): 3446m, 3291w, 3253w, 3145s, 1588s, 1538s, 1486s,
1453m, 1408m, 1377m, 1343s, 1316w, 1228s, 1143s, 1082m, 1041w, 1026w, 998s, 961m, 884m, 837w, 812w,
789s. 1H-NMR (300 MHz, (D6)DMSO): 10.66, 7.72 (2 br. s, H2NꢀC(6)); 7.36 – 7.25 (m, 5 arom. H); 7.19
(br. s, H2NꢀC(2)); 5.15 (s, PhCH2); 3.35 (s, NMe). 13C-NMR (75 MHz, (D6)DMSO): 162.83, 162.11 (2s,
C(2), C(4)); 151.54 (s, C(6)); 141.27 (s, C(5)); 137.33 (s, C(1’)); 128.09 (d, C(2’), C(6’)); 126.92 (d, C(3’),
C(5’)); 126.64 (d, C(4’)); 63.39 (t, PhCH2); 39.99 (q, NMe). HR-MALDI-MS: 225.1304 (39, [M þ H]þ,
C12H15N6Oþ; calc. 259.1307), 241.1201 (99, [M ꢀ OH]þ, C12H13N6þ ; calc. 241.1202), 228.1249 (100, [M ꢀ
NO]þ, C12H14N5þ ; calc. 228.1249). Anal. calc. for C12H14N6O (258.28): C 55.80, H 5.46, N 32.54; found: C
55.91, H 5.37, N 32.21.
N4-Ethyl-N4-(1-methylethyl)-5-nitrosopyrimidine-2,4,6-triamine (9). Prepared according to GP 1
from 3 (500 mg, 2.02 mmol) and ethyl(isopropyl)amine (488 ml, 4.04 mmol) at 608 for 90 min. Yield:
312 mg (68%). Rf (CH2Cl2/MeOH 9 :1) 0.51. M.p. 2148. IR (ATR): 3301w, 3142s, 1629s, 1531w, 1504w,
1378m, 1322s, 1250s, 1203w, 1151s, 1104s, 1044m, 994m, 916w, 792s, 751m. 1H-NMR (300 MHz,
(D6)DMSO): 10.78, 7.63 (2 br. s, H2NꢀC(6)); 7.04 (br. s, H2NꢀC(2)); 5.22 (br. s, CHMe2); 3.74 (br. q, J ¼
6.9, CH2Me); 1.22 – 1.15 (m, NHMe2, NCH2Me). 13C-NMR (75 MHz, (D6)DMSO): 161.88, 161.72 (2s,
C(2), C(4)); 151.67 (s, C(6)); 141.06 (s, C(5)); 40.13 (d, CHMe2); 39.56 (t, CH2Me): 20.54 (q, CHMe2);
15.66 (q, CH2Me). HR-MALDI-MS: 225.1461 (48, [M þ H]þ, C9H17N6Oþ; calc. 225.1464), 207.1352 (100,
[M ꢀ OH]þ, C9H15Nþ6 ; calc. 207.1358), 194.1400 (14, [M ꢀ NO]þ, C9H16Nþ5 ; calc. 194.1406).
5-Nitroso-6-(pyrrolidin-1-yl)pyrimidine-2,4-diamine (10) [21]. Prepared similarly to 4 according to
GP 1 from 3 (500 mg, 2.02 mmol) and pyrrolidine (332 ml, 4.04 mmol). Yield: 361 mg (86%). Red
powder. Rf (CH2Cl2/MeOH 9 :1) 0.46. M.p. 2548 ([21]: 233 – 2348). IR (ATR): 3146w, 2972s, 2873w,
1606m, 1539s, 1476s, 1371s, 1337m, 1310s, 1256m, 1227m, 1206s, 1141s, 1054m, 1033m, 996s, 921w, 881m,
1
838w, 789s. H-NMR (300 MHz, (D6)DMSO): 10.76, 7.63 (2 br. s, H2NꢀC(4)); 7.05 (br. s, H2NꢀC(2));
3.77 (br. s, 2 HꢀC(2’), 2 HꢀC(5’)); 1.88 (br. s, 2 HꢀC(3’), 2 HꢀC(4’)). 13C-NMR (75 MHz, (D6)DMSO):
162.17 (s, C(2)); 160.59 (s, C(6)); 151.46 (s, C(4)); 141.14 (s, C(5)); 52.67, 49.73 (2t, C(2’), C(5’)); 26.32,
23.34 (2t, C(3’), C(4’)). HR-MALDI-MS: 209.1145 (53, [M þ H]þ, C8H13N6Oþ; calc. 209.1151), 191.1043
(100, [M ꢀ OH]þ, C8H11Nþ6 ; calc. 191.1045).
5-Nitroso-6-(piperidin-1-yl)pyrimidine-2,4-diamine (11) [21][22][29]. Prepared similarly to 4
according to GP 1 from 3 (500 mg, 2.02 mmol) and piperidine (399 ml, 4.04 mmol) (192 mg, 85%).
Pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.52. M.p. 2108 ([21][22][29]: 211.5 – 2148). IR (ATR): 3477m,
3404m, 3253w, 3049s, 2937w, 2850w, 1648w, 1610m, 1536s, 1478s, 1442s, 1436s, 1337s, 1301s, 1237s, 1179m,
1
1154s, 1108s, 1068w, 1051m, 1008m, 982s, 869w. H-NMR (300 MHz, (D6)DMSO): 10.56, 7.64 (2 br. s,
H2NꢀC(4)); 7.11 (br. s, H2NꢀC(2)); 3.98 (d, J ¼ 5.1, 2 HꢀC(2’), 2 HꢀC(6’)); 1.68 – 1.59 (m, 2 HꢀC(3’),
2 HꢀC(4’), 2 HꢀC(5’)). 13C-NMR (75 MHz, (D6)DMSO): 162.23, 161.95 (2s, C(2), C(6)); 151.58 (s,
C(4)); 140.67 (s, C(5)); 49.19 (t, C(2’), C(6’)); 26.31 (t, C(3’), C(5’)); 24.37 (t, C(4’)). HR-MALDI-MS:
223.1302 (72, [M þ H]þ, C9H15N6Oþ; calc. 223.1307), 191.1047 (100, [M ꢀ HNO]þ, C9H13Nþ5 ; calc.
191.1171).
6-(Azepan-1-yl)-5-nitrosopyrimidine-2,4-diamine (12). Prepared according to GP 1 from 3 (500 mg,
2.02 mmol) and azepane (455 ml, 4.04 mmol) at 608 for 50 min. Yield: 335 mg (72%). Pink powder. Rf
(CH2Cl2/MeOH 9 :1) 0.55. M.p. 2248. IR (ATR): 3315m, 3145s, 2980w, 2934m, 2857w, 1629s, 1555w, 1535s,

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1475s, 1460w, 1431s, 1374m, 1364w, 1332s, 1314s, 1283w, 1252w, 1241s, 1223s, 1186w, 1173w, 1136s, 1101m,
1
1064m, 1033m, 1011m, 999s, 978m, 902m, 863w. H-NMR (300 MHz, (D6)DMSO): 10.65, 7.63 (2 br. s,
H2NꢀC(4)); 7.04 (br. s, H2NꢀC(2)); 3.95 (t, J ¼ 6.0, 2 HꢀC(2’), 2 HꢀC(7’)); 1.72 (br. s, 2 HꢀC(3’),
2 HꢀC(6’)); 1.54 (br. s, 2 HꢀC(4’), 2 HꢀC(5’)). 13C-NMR (75 MHz, (D6)DMSO): 162.02, 161.79 (2d,
C(2), C(6)); 151.60 (d, C(4)); 141.98 (d, C(5)); 52.60 (t, C(2’), C(7’)); 27.79 (t, C(3’), C(6’)); 26.09 (t,
C(4’), C(5’)). HR-MALDI-MS: 237.1849 (50, [M þ H]þ, C10H17N6Oþ; calc. 237.1853), 219.1363 (100,
[M ꢀ OH]þ, C10H15Nþ6 ; calc. 219.1358).
6-(3,4-Dihydroisoquinolin-2(1H)-yl)-5-nitrosopyrimidine-2,4-diamine (13). Prepared similarly to 4
according to GP 1 from 3 (500 mg, 2.02 mmol) and 1,2,3,4-tetrahydroquinoline (508 ml, 4.04 mmol).
Yield: 518 mg (95%). Pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.47. M.p. 1308. IR (ATR): 3394w, 3317m,
3135s, 2833w, 1652s, 1595s, 1523s, 1490s, 1457w, 1440s, 1428w, 1381w, 1342s, 1316s, 1281m, 1219s, 1197m,
1
1141s, 1052s, 999s, 978s, 932m, 883w, 862w, 832w, 809w, 789s. H-NMR (300 MHz, (D6)DMSO): 10.55,
7.73 (2 br. s, H2NꢀC(4)); 7.26 – 7.16 (m, 4 arom. H, H2NꢀC(2)); 5.12 (s, 2 HꢀC(1’)); 4.16 (t, J ¼ 5.7,
2 HꢀC(3’)); 2.94 (t, J ¼ 5.7, 2 HꢀC(4’)). 13C-NMR (75 MHz, (D6)DMSO): 162.59, 162.14 (2s, C(2), C(6));
151.51 (s, C(4)); 140.93 (s, C(5)); 134.68, 133.54 (2s, C(4a’), C(8a’)); 128.01, 126.18 (2d, C(5’), C(8’));
125.89, 125.78 (2d, C(6’), C(7’)); 55.03 (t, C(1’)); 46.75 (t, C(3’)); 28.72 (t, C(4’)). HR-MALDI-MS:
271.1302 (45, [M þ H]þ, C13H15N6Oþ; calc. 271.1307), 253.1198 (73, [M ꢀ OH]þ; C13H13Nþ6 ; calc.
253.1202), 240.1244 (100, [M ꢀ NO]þ, C13H14N5þ ; calc. 240.1249).
6-(1,4’-Bipiperidin-1’-yl)-5-nitrosopyrimidine-2,4-diamine (14). Prepared according to GP 1 from 3
(500 mg, 2.02 mmol) and 4-(piperidin-1-yl)piperidine (700 ml, 4.04 mmol) at 608 for 120 min. Yield:
587 mg (95%). Pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.60. M.p. 2358. IR (ATR): 3220m, 3138m, 2972s,
2846w, 2800w, 1651w, 1612s, 1537s, 1483s, 1450s, 1425m, 1394w, 1330s, 1236s, 1216m, 1166w, 1143s, 1120s,
1057m, 1033m, 1013s, 986s, 932w, 873m, 829m, 788s, 749m. 1H-NMR (300 MHz, (D6)DMSO): 10.53, 7.67
(2 br. s, H2NꢀC(4)); 7.14 (br. s, H2NꢀC(2)); 4.91 (br. d, J ¼ 12.3, HaꢀC(2’), Haꢀ(C6’)); 3.08 (br. t, J ¼ 12.3,
HbꢀC(2’), HbꢀC(6’)); 2.64 – 2.45 (m, HꢀC(4’), 2 HꢀC(2’’), 2 HꢀC(6’’)); 1.79 (d, J ¼ 11.7, HaꢀC(3’),
HaꢀC(5’)); 1.45 – 1.38 (m, HbꢀC(3’), HbꢀC(5’), 2 HꢀC(3’’), 2 HꢀC(4’’), 2 HꢀC(5’’)). 13C-NMR (75 MHz,
(D6)DMSO): 162.28 (s, C(2)); 161.99 (s, C(6)); 151.54 (s, C(4)); 140.67 (s, C(5)); 61.60 (t, C(2’), C(6’));
49.60 (t, C(2’’), C(6’’)); 47.67 (d, C(4’)); 28.32 (t, C(3’), C(5’)); 26.09 (t, C(3’’), C(5’’)); 24.58 (t, C(4’’)).
HR-MALDI-MS: 306.2038 (100, [M þ H]þ, C14H24N7Oþ; calc. 306.2042), 288.1922 (54, [M ꢀ OH]þ,
C14H22Nþ7 ; calc. 288.1937), 275.1978 (54, [M ꢀ NO]þ, C14H23N6þ ; calc. 275.1984). Anal. calc. for
C14H23N7O (305.38): C 55.06, H 7.59, N 32.11; found: C 54.78, H 7.41, N 31.75.
Ethyl 1-(2,6-Diamino-5-nitrosopyrimidin-4-yl)piperidine-4-carboxylate (15). Compound 15 was
prepared similarly to 14 according to GP 1 from 3 (500 mg, 2.02 mmol) and ethyl isonipecotate
(611 ml, 4.04 mmol). Yield: 389 mg (65%). Red powder. Rf (CH2Cl2/MeOH 9 :1) 0.62. M.p. 2478. IR
(ATR): 3428m, 3305m, 3174m, 2981s, 2765w, 1716s, 1606s, 1537s, 1476m, 1394w, 1375w, 1318s, 1204s,
1177m, 1138s, 1095m, 1046m, 1033s, 1012s, 948w, 936w, 865m, 826w, 789s, 692s. 1H-NMR (300 MHz,
(D6)DMSO): 10.51, 7.69 (2 br. s, H2NꢀC(6)); 7.17 (br. s, H2NꢀC(2)); 4.07 (q, J ¼ 7.2, OCH2Me); 3.59 –
3.29 (m, 2 HꢀC(2’), 2 HꢀC(6’)); 2.75 – 2.73 (m, HꢀC(4’)); 1.92 (t, J ꢁ 9.9, HaꢀC(3’), HaꢀC(5’)); 1.63 (q,
J ¼ 10.2, HbꢀC(3’), HbꢀC(5’)); 1.19 (t, J ¼ 7.2, OCH2Me). 13C-NMR (75 MHz, (D6)DMSO): 173.38 (s,
C¼O); 162.33, 162.28 (2s, C(2), C(4)); 151.51 (s, C(6)); 140.70 (s, C(5)); 59.86 (t, OCH2Me); 47.39 (t,
C(2’), C(6’)); 28.43 (t, C(3’), C(5’)); 26.31 (d, C(4’)); 14.15 (q, OCH2Me). HR-MALDI-MS: 295.1516 (50,
[M þ H]þ, C12H19N6O3þ ; calc. 295.1519), 277.1409 (100, [M ꢀ OH]þ, C12H17N6Oþ2 ; calc. 277.1408),
264.1459 (18, [M ꢀ NO]þ, C12H18N5Oþ2 ; calc. 264.1460). Anal. calc. for C12H18N6O3 (294.31): C 48.87, H
6.16, N 28.55; found: C 48.47, H 6.35, N 28.27.
6-(Morpholin-4-yl)-5-nitrosopyrimidine-2,4-diamine (16) [21]. Compound 16 was prepared accord-
ing to GP 1 from 3 (500 mg, 2.02 mmol) and morpholine (355 mml, 4.04 mmol) at 608 for 150 min. Yield:
361 mg (68%). Red-orange powder. Rf (CH2Cl2/MeOH 9 :1) 0.40. M.p. 2468 ([21]: 225 – 2268). IR
(ATR): 3488s, 3430m, 3316m, 3030m, 2919s, 2851m, 1604s, 1546w, 1517m, 1487s, 1461w, 1421w, 1374s,
1
1324s, 1267m, 1225w, 1216s, 1159s, 1111m, 1099s, 1059w, 1026m, 987s, 919w, 865s, 827w, 787s. H-NMR
(300 MHz, (D6)DMSO): 10.52, 7.74 (2 br. s, H2NꢀC(4)); 7.29 (br. s, H2NꢀC(2)); 4.04 (t, J ¼ 4.5,
2 HꢀC(2’), 2 HꢀC(6’)); 3.69 (t, J ¼ 4.6, 2 HꢀC(3’), 2 HꢀC(5’)). 13C-NMR (75 MHz, (D6)DMSO): 165.22
(s, C(6)); 162.19 (s, C(2)); 151.49 (s, C(4)); 140.78 (s, C(5)); 66.34 (t, C(2’), C(6’)); 48.58 (t, C(3’), C(5’)).

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Helvetica Chimica Acta – Vol. 94 (2011)
HR-MALDI-MS: 225.1092 (78, [M þ H]þ, C8H13N6O2þ ; calc. 225.1100), 207.0989 (100, [M ꢀ OH]þ,
C8H11N6Oþ, calc. 207.0994).
Diethyl 2,2’-[(2,6-Diamino-5-nitrosopyrimidin-4-yl)imino]diacetate (17). Compound 17 was pre-
pared according to GP 1 from 3 (100 mg, 0.4 mmol) and diethyl iminodiacetate (142 ml, 0.81 mmol) at 908
for 140 min. Yield: 59.5 mg (45%). Pink powder. Rf (CH2Cl2/MeOH 9 :1) 0.63. M.p. 1508. IR (ATR):
3400m, 3275m, 3125s, 2998w, 2928w, 1733s, 1625s, 1527s, 1489w, 1441w, 1407w, 1370m, 1353w, 1315m,
1
1238m, 1210s, 1187s, 1140s, 1057m, 1016s, 980s, 869w, 788m, 748m. H-NMR (300 MHz, (D6)DMSO):
10.46, 7.82 (2 br. s, H2NꢀC(6)); 7.30, 7.19 (2 br. s, H2NꢀC(2)); 4.54 (s, N(CH2)2); 4.13, 4.03 (2q, J ¼ 7.2,
2 OCH2Me); 1.23 – 1.13 (m, 2 OCH2Me). 13C-NMR (75 MHz, (D6)DMSO): 168.56, 168.23 (2s, 2 C¼O);
162.82, 161.80 (2s, C(2), C(4)); 151.17 (s, C(6)); 140.90 (s, C(5)); 60.43, 60.01 (2t, N(CH2)2, 2 OCH2Me);
14.16 (q, 2 OCH2Me). HR-MALDI-MS: 327.1407 (35, [M þ H]þ, C12H19N6O5þ ; calc. 327.1417), 309.1297
(17, [M ꢀ OH]þ, C12H17N6O4þ ; calc. 309.1311), 296.1348 (100, [M ꢀ NO]þ, C12H18N5Oþ4 ; calc. 296.1359).
1-Phenylimidazolidine. According to [23], a soln. of N-phenylethane-1,2-diamine (1 g, 7.34 mmol) in
EtOH (2 ml) was treated dropwise at r.t. with 37% aq. HCHO (3.30 g, 11 mmol), and stirred for 10 min
until TLC showed disappearance of the diamine. Upon cooling to 58, a pale precipitate was formed which
was filtered off, washed with H2O, and dried under vacuum to afford the title compound (856 mg, 80%).
Rf (CH2Cl2/MeOH 9 :1) 0.48. M.p. 1208. IR (ATR): 3344s, 3054s, 2920w, 2859w, 2796s, 2709w, 1661s,
1599s, 1568w, 1509s, 1462m, 1415w, 1384m, 1367m, 1323w, 1258w, 1230s, 1207w, 1191w, 1154m, 1104w,
1075w, 1033m, 982s, 967w, 923m, 859m. 1H-NMR (300 MHz, (D6)DMSO): 7.24 (t, J ¼ 7.6, HꢀC(3’),
HꢀC(5’)); 6.71 (t, J ¼ 7.5, HꢀC(4’)); 6.53 (d, J ¼ 7.8, HꢀC(2’), HꢀC(6’)); 4.17 (s, 2 HꢀC(2)); 3.44 (t, J ¼
6.6, 2 HꢀC(5)); 3.14 (t, J ¼ 6.3, 2 HꢀC(4)); 2.18 (br. s, NH). 13C-NMR (75 MHz, (D6)DMSO): 146.3 (s,
C(1’)); 129.26 (d, C(3’), C(5’)); 116.41 (d, C(4’)); 111.74 (d, C(2’), C(6’)); 69.07 (t, C(2)); 50.95 (t, C(5));
45.73 (t, C(4)). HR-MALDI-MS: 149.1072 (100, [M þ H]þ, C9H13N2þ ; calc. 149.1079).
5-Nitroso-6-(3-phenylimidazolidin-1-yl)pyrimidine-2,4-diamine (18). Compound 18 was prepared
according to GP 1 from 3 (100 mg, 0.4 mmol) and 1-phenylimidazolidine (120 mg, 0.81 mmol) at 908 for
120 min. Yield: 37 mg (32%). Pink-violet powder. Rf (CH2Cl2/MeOH 9 :1) 0.49. M.p. 1828. IR (ATR):
3310m, 3131s, 3070s, 2985s, 1666w, 1629s, 1539s, 1496s, 1367w, 1322s, 1247s, 1145s, 997w, 916m, 808w, 788s.
1H-NMR (300 MHz, (D6)DMSO): 10.64, 7.80 (br. s, H2NꢀC(4)); 7.40 – 7.20 (m, H2NꢀC(2), HꢀC(3’’),
HꢀC(5’’)); 6.79 (t, J ¼ 7.2, HꢀC(4’’)); 6.69 (br. s, HꢀC(2’’), HꢀC(6’’)); 5.03 (s, 2 HꢀC(2’)); 4.14 (br. s,
HꢀC(5’)); 3.54 (br. s, HꢀC(4’)). 13C-NMR (75 MHz, (D6)DMSO): 162.27 (br. s, C(2), C(4)); 151.25 (s,
C(6)); 145.99 (s, C(1’’)); 140.85 (s, C(5)); 128.82 (d, C(3’’), C(5’’)); 117.91 (d, C(4’’)); 113.19 (d, C(2’’),
C(6’’)); 68.22 (t, C(2’)); 47.39 (t, C(5’)); 44.09 (t, C(4’)). HR-MALDI-MS: 268.1311 (30, [M ꢀ OH]þ,
C13H14Nþ7 ; calc. 268.1305), 255.1442 (100, [M ꢀ NO]þ, C13H16Nþ6 ; calc. 255.1431).
General Procedure for Thermal Cyclisation of 4-(Dialkylamino)-5-nitroso-pyrimidines (GP 2). A
suspension of the nitroso amines 4 – 18 in Ph2O (1 – 3 ml) was heated to 175 – 2108 until LC/MS showed
completion of the reaction (see the Table). Flash column chromatography (pentane for removal of Ph2O,
then MeCN/EtOH 1:2 to 1:1) gave the products 19 – 32.
9-Methyl-9H-purine-2,6-diamine (19) [10]. Yield: 97%. Rf (CH2Cl2/MeOH 5 :1) 0.29. M.p. 2908
([10]: 314 – 316 (dec.)). IR (ATR): 3312m, 3109s, 2929w, 1662w, 1631m, 1587s, 1527m, 1474w, 1454w,
1429m, 1404s, 1336s, 1284m, 1216m, 1102m, 1053m, 977m, 860w, 833w, 790s. 1H-NMR (300 MHz,
(D6)DMSO): 7.64 (s, HꢀC(8)); 6.61 (br. s, H2NꢀC(6)); 5.76 (br. s, H2NꢀC(2)); 3.53 (s, MeN). 13C-NMR
(75 MHz, (D6)DMSO): 159.80 (s, C(6)); 155.55 (s, C(2)); 151.65 (s, C(4)); 137.54 (d, C(8)); 112.78 (s,
C(5)); 28.95 (q, NMe). HR-MALDI-MS: 165.0885 (100, [M þ H]þ, C6H9N6þ ; calc. 165.0889).
9-Ethyl-8-methyl-9H-purine-2,6-diamine (20). Yield: 95%. Rf (CH2Cl2/MeOH 5 :1) 0.43. M.p. 2528.
IR (ATR): 3492m, 3293w, 3114m, 2971w, 2937w, 1663m, 1630s, 1589s, 1479s, 1446m, 1417s, 1384s, 1371s,
1337s, 1273w, 1249w, 1167w, 1065w, 1035w, 1005m, 961w, 829w, 792s, 771m. 1H-NMR (300 MHz,
(D6)DMSO): 6.46 (br. s, H2NꢀC(6)); 5.65 (br. s, H2NꢀC(2)); 3.94 (q, J ¼ 7.2, NCH2Me); 2.39 (s, Me); 1.23
(t, J ¼ 7.1, NCH2Me). 13C-NMR (75 MHz (D6)DMSO): 159.22 (s, C(6)); 154.62 (s, C(2)); 152.00 (s, C(4));
143.96 (s, C(8)); 111.55 (s, C(5)); 36.24 (t, NCH2Me); 14.97 (q, NCH2Me); 13.39 (q, Me). HR-MALDI-
MS: 193.1106 (100, [M þ H]þ, C8H13N6þ ; calc. 193.1206).
8,9-Dimethyl-9H-purine-2,6-diamine (21). Yield: 95%. Rf (CH2Cl2/MeOH 5 :1) 0.35. M.p. 2928. IR
1
(ATR): 3314m, 3126s, 1630w, 1593s, 1432w, 1406s, 1380s, 1357w, 1335m, 1065w, 986m, 788s. H-NMR
(300 MHz, (D6)DMSO): 6.46 (br. s, H2NꢀC(6)); 5.64 (br. s, H2NꢀC(2)); 3.27 (s, NMe); 2.36 (s,

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MeꢀC(8)). 13C-NMR (75 MHz, (D6)DMSO): 159.16 (s, C(6)); 154.55 (s, C(2)); 152.49 (s, C(4)); 144.82
(s, C(8)); 111.44 (s, C(5)); 27.89 (q, NMe); 13.39 (q, MeꢀC(8)). HR-MALDI-MS: 179.1088 (100, [M þ
H]þ, C7H11Nþ6 ; calc. 179.1045).
9-Methyl-8-propyl-9H-purine-2,6-diamine (22). Yield: 94%. Rf (CH2Cl2/MeOH 5 :1) 0.65. M.p. 2458.
IR (ATR): 3312m, 3144m, 2961w, 2929w, 2876w, 1627w, 1589s, 1437s, 1403m, 1380s, 1333m, 1284w, 1156w,
1082w, 993m, 938w, 790s. 1H-NMR (300 MHz, (D6)DMSO): 6.47 (br. s, H2NꢀC(6)); 5.65 (br. s,
H2NꢀC(2)); 3.46 (s, MeN); 2.69 (t, J ¼ 7.5, CH2ꢀC(8)); 1.72 (sext., J ¼ 7.5, CH2Me); 0.97 (t, J ¼ 7.3,
CH2Me). 13C-NMR (75 MHz, (D6)DMSO): 155.97 (s, C(6)); 154.66 (s, C(2)); 152.53 (s, C(4)); 147.90 (s,
C(8)); 111.61 (s, C(5)); 28.62 (q, MeN); 27.84 (t, CH2ꢀC(8)); 20.28 (t, CH2Me); 13.86 (q, CH2Me). HR-
MALDI-MS: 207.1353 (100, [M þ H]þ, C9H15N6þ ; calc. 207.1358).
9-Methyl-8-phenyl-9H-purine-2,6-diamine (23). Yield: 88%. Rf (CH2Cl2/MeOH 5 :1) 0.71. M.p. 2928.
IR (ATR): 3465m, 3331m, 3172m, 2989w, 2916w, 1655w, 1622s, 1588s, 1517m, 1503m, 1462s, 1431s, 1406s,
1340s, 1313w, 1289w, 1211w, 1184w, 1149w, 1100w, 1061m, 1024m, 974m, 920w, 850w, 790s, 775s. 1H-NMR
(300 MHz, (D6)DMSO): 7.78 (d, J ¼ 6.9, HꢀC(2’), HꢀC(6’)); 7.55 – 7.40 (m, HꢀC(3’), HꢀC(4’),
HꢀC(5’)); 6.73 (br. s, H2NꢀC(6)); 5.84 (br. s, H2NꢀC(2)); 3.64 (s, MeN). 13C-NMR (75 MHz,
(D6)DMSO): 159.78 (s, C(6)); 155.46 (s, C(2)); 153.53 (s, C(4)); 146.01 (s, C(8)); 130.10 (d, C(4’)); 128.54
(s, C(1’)); 128.18 (d, C(2’), C(6’)); 128.05 (d, C(3’), C(5’)); 112.81 (s, C(5)); 30.08 (q, MeN). HR-
MALDI-MS: 241.1198 (100, [M þ H]þ, C12H13N6þ ; calc. 241.1202).
7,8-Dihydro-6H-pyrrolo[1,2-e]purine-2,4-diamine (24). Yield: 92%. Rf (CH2Cl2/MeOH 5 :1) 0.29.
M.p. 3348. IR (ATR): 3476m, 3286m, 3107s, 1671m, 1633m, 1582s, 1466m, 1424s, 1383s, 1329w, 1302m,
1272w, 1173w, 1062m, 1018m, 784s. 1H-NMR (300 MHz, (D6)DMSO): 6.44 (br. s, H2NꢀC(4)); 5.64 (br. s,
H2NꢀC(2)); 3.85 (t, J ¼ 6.7, 2 HꢀC(8)); 2.77 (t, J ¼ 7.5, 2 HꢀC(6)); 2.55 (quint., J ¼ 6.9, 2 HꢀC(7)).
13C-NMR (75 MHz, (D6)DMSO): 158.94 (s, C(4)); 154.75 (s, C(2)); 153.77 (s, C(9a)); 149.59 (s, C(5a));
117.11 (s, C(4a)); 41.1 (t, C(8)); 25.86 (t, C(6)); 22.42 (t, C(7)). HR-MALDI-MS: 191.1039 (100, [M þ
H]þ, C8H11Nþ6 ; calc. 191.1045).
6,7,8,9-Tetrahydropyrido[1,2-e]purine-2,4-diamine (25). Yield: 95%. Rf (CH2Cl2/MeOH 5 :1) 0.35.
M.p. 3098. IR (ATR): 3483m, 3297m, 3122s, 2945w, 1671m, 1632m, 1585s, 1474w, 1457w, 1417s, 1387s,
1350s, 1325s, 1272m, 1240w, 1171w, 1148w, 1109w, 1074w, 1022w, 965w, 954m, 914w, 870w, 822w, 788s.
1H-NMR (300 MHz, (D6)DMSO): 6.47 (br. s, H2NꢀC(4)); 5.66 (br. s, H2NꢀC(2)); 3.82 (t, J ¼ 5.7,
2 HꢀC(9)); 2.79 (t, J ¼ 6.1, 2 HꢀC(6)); 1.93 – 1.88 (m, 2 HꢀC(7), 2 HꢀC(8)). 13C-NMR (75 MHz,
(D6)DMSO): 159.09 (s, C(4)); 154.61 (s, C(2)); 151.55 (s, C(10a)); 144.27 (s, C(5a)); 111.72 (s, C(4a));
41.04 (t, C(9)); 24.92 (t, C(6)); 22.04 (t, C(8)); 20.43 (t, C(7)). HR-MALDI-MS: 205.1197 (100, [M þ H]þ,
C9H13Nþ6 ; calc. 205.1202).
7,8,9,10-Tetrahydro-6H-azepino[1,2-e]purine-2,4-diamine (26). Yield: 96%. Rf (CH2Cl2/MeOH 5 :1)
0.34. M.p. 3058. IR (ATR): 3472m, 3296m, 3108s, 2927s, 2852w, 1668m, 1610m, 1583s, 1469m, 1430w,
1417s, 1389s, 1361w, 1348s, 1322m, 1279w, 1257w, 1226m, 1190m, 1141w, 1085m, 1067w, 1029w, 1006w,
965s, 893w, 883w, 837w, 823w, 790s. 1H-NMR (300 MHz, (D6)DMSO): 6.47 (br. s, H2NꢀC(4)); 5.62 (br. s,
H2NꢀC(2)); 4.01 (br. s, 2 HꢀC(10)); 2.88 – 2.80 (m, 2 HꢀC(6)); 1.83 – 1.76 (m, 2 H), 1.65 – 1.60 (m, 4 H)
(2 HꢀC(7), 2 HꢀC(8), 2 HꢀC(9)). 13C-NMR (75 MHz, (D6)DMSO): 159.19 (s, C(4)); 154.87 (s, C(2));
152.13 (s, C(5a)); 150.19 (s, C(11a)); 117.14 (s, C(4a)); 41.62 (t, C(10)); 30.27 (t, C(6)); 29.40, 28.51, 25.78
(3t, C(7), C(8), C(9)). HR-MALDI-MS: 219.1350 (100, [M þ H]þ, C10H15N6þ ; calc. 219.1358).
X-Ray Data of 26 · DMSO. Crystals of 26 · DMSO suitable for X-ray analysis were obtained by
isothermal distillation of H2O in a soln. of 26 in DMSO. Crystal data at 123 K for C10H14N6 · C2H6OS
(296.4); monoclinic P21/c; a ¼ 12.9469(6), b ¼ 8.4516(4), c ¼ 13.1139(7) ꢄ, b ¼ 90.320(2)8. V¼
1434.93(12) ꢄ3 ; Z ¼ 4; Dcalc ¼ 1.372 Mg/m3. Bruker-Nonius Kappa-CCD with MoKa radiation (l ¼
0.71073 ꢄ). The structure was solved by direct methods [30] and refined by full-matrix least-squares
analysis [31] including an isotropic extinction correction. All heavy atoms were refined anisotropically
(H-atoms isotropic, whereby H-positions are based on stereochemical considerations). R ¼ 0.0994, Rw ¼
0.1756 for 261 parameters and 3254 reflections with I > 2s(I).
5,6-Dihydropurino[8,9-a]isoquinoline-9,11-diamine (27). Yield: 95%. Rf (CH2Cl2/MeOH 5 :1) 0.58.
M.p. 3028. IR (ATR): 3309w, 3124s, 1633m, 1587s, 1574s, 1527m, 1477w, 1452w, 1418s, 1385s, 1333s, 1299w,
1278w, 1154w, 1074w, 1047m, 984s, 903s, 805m, 789s, 773s. 1H-NMR (300 MHz, (D6)DMSO): 7.93 (d, J ¼
7.5, HꢀC(1)); 7.39 (t, J ¼ 7.5, HꢀC(3)); 7.13 (t, J ¼ 7.4, HꢀC(2)); 7.01 (d, J ¼ 7.5, HꢀC(4)); 6.76 (br. s,

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Helvetica Chimica Acta – Vol. 94 (2011)
H2NꢀC(11)); 5.88 (br. s, H2NꢀC(9)); 4.11 (t, J ¼ 6.9, 2 HꢀC(6)); 3.17 (t, J ¼ 6.8, 2 HꢀC(5)). 13C-NMR
(75 MHz, (D6)DMSO): 159.51 (s, C(11)); 155.17 (s, C(9)); 151.49 (s, C(7a)); 141.97 (s, C(4a)); 134.13 (s,
C(12a)); 128.65, 128.12 (2d, C(2), C(3)); 126.86, 123.02 (2d, C(1), C(4)); 113.58 (s, C(11a)); 55.93 (t,
C(6)); 27.45 (t, C(5)). HR-MALDI-MS: 253.1194 (100, [M þ H]þ, C13H13N6þ ; calc. 253.1202).
X-Ray Data of 27 · 1.5 H2O · 0.5 DMSO. Crystals of 27 · 1.5 H2O · 0.5 DMSO suitable for X-ray
analysis were obtained upon storing a soln. of 27 in DMSO for an extended period of time. Crystal data at
100 K for 2 C13H12N6 · 3 H2O · C2H6OS (636.749); monoclinic P21/c; a ¼ 18.0070(6), b ¼ 6.9897(3), c ¼
23.4261(9) ꢄ, b ¼ 90.8293(12)8. V ¼ 2948.2(2) ꢄ3 ; Z ¼ 4. Bruker-Nonius Kappa-CCD with MoKa
radiation (l ¼ 0.7107 ꢄ). The structure was solved by direct methods [30] and refined by full-matrix
least-squares analysis [31] including an isotropic extinction correction. All heavy atoms were refined
anisotropically (H-atoms isotropic, whereby H-positions are based on stereochemical considerations).
R ¼ 0.0813, Rw ¼ 0.1612 for 550 parameters and 4512 reflections with I > 2s(I).
(ꢂ)-6,7,8,9-Tetrahydro-7-(piperidin-1-yl)pyrido[1,2-e]purine-2,4-diamine ((ꢂ)-28). Yield: 89%. Rf
(CH2Cl2/MeOH 5 :1) 0.36. M.p. 2528. IR (ATR): 3315m, 3113m, 2926s, 1727w, 1667w, 1631m, 1593s,
1478m, 1421m, 1387s, 1333s, 1269w, 1205m, 1151w, 1072m, 1017m, 1000s, 995m, 789s. 1H-NMR
(300 MHz, (D6)DMSO): 6.46 (br. s, H2NꢀC(4)); 5.64 (br. s, H2NꢀC(2)); 4.01 – 3.96 (m, HaꢀC(9)); 3.68
(td, J ꢁ 10.6, 4.8, HbꢀC(9)); 2.87 (narrow AB, 2 HꢀC(6)); 2.59 – 2.46 (m, HꢀC(7), 2 HꢀC(2’), 2 HꢀC(6’));
2.18 – 2.08 (m, 1 H); 2.00 – 1.85 (m, 1 H); 1.55 – 1.35 (m, 6 H). 13C-NMR (75 MHz, (D6)DMSO): 159.16
(s, C(4)); 154.61 (s, C(2)); 151.41 (s, C(10a)); 144.33 (s, C(5a)); 112.05 (s, C(4a)); 57.85 (d, C(7)); 49.64 (t,
C(2’), C(6’)); 27.56 (t, C(8)); 25.85 (t, C(3’), C(5’)); 24.34 (t, C(4’)); signals for C(6) and C(9) hidden by
the solvent signals. HR-MALDI-MS: 288.1930 (100, [M þ H]þ, C14H22N7þ ; calc. 288.1937).
Ethyl (ꢂ)-2,4-Diamino-6,7,8,9-tetrahydropyrido[1,2-e]purine-7-carboxylate ((ꢂ)-29). Yield: 92%. Rf
(CH2Cl2/MeOH 5 :1) 0.32. M.p. 2798. IR (ATR): 3421m, 3300w, 3180s, 2989w, 1714s, 1645w, 1628m, 1590s,
1526w, 1470s, 1436m, 1422s, 1391s, 1369m, 1331s, 1294m, 1254s, 1209m, 1122w, 1071w, 1036m, 1017w,
936w, 904m, 871m, 847w, 790s, 775w. 1H-NMR (300 MHz, (D6)DMSO): 6.52 (br. s, H2NꢀC(4)); 5.68 (br.
s, H2NꢀC(2)); 4.13 (q, J ¼ 6.9, OCH2Me)); 4.00 – 3.90 (m, HaꢀC(9)); 3.90 – 3.75 (m, HbꢀC(9)); 3.07 – 2.88
(m, 2 HꢀC(6), HꢀC(7)); 2.33 – 2.29 (m, HaꢀC(8)); 2.09 – 2.03 (m, HbꢀC(8)); 1.21 (t, J ¼ 7.1, OCH2Me).
13C-NMR (75 MHz, (D6)DMSO): 172.63 (s, C¼O); 159.22 (s, C(4)); 154.71 (s, C(2)); 151.45 (s, C(10a));
142.78 (s, C(5a)); 111.96 (s, C(4a)); 60.33 (t, OCH2Me); 40.13 (t, C(9)); 36.94 (d, C(7)); 27.08, 24.80 (2t,
C(6), C(8)); 14.14 (q, OCH2Me). HR-MALDI-MS: 277.1405 (100, [M þ H]þ, C12H17N6O2þ ; calc.
277.1413).
8,9-Dihydro-6H-[1,4]oxazino[4,3-e]purine-2,4-diamine (30). Yield: 85%. Rf (CH2Cl2/MeOH 10 :1)
0.29. M.p. 3628. IR (ATR): 3384w, 3223s, 3173s, 2957w, 2884w, 2843w, 1638m, 1585s, 1464s, 1421s, 1393s,
1337s, 1291w, 1262w, 1221w, 1147w, 1107m, 1092s, 1024w, 1000w, 974s, 946m, 872m, 858m. 1H-NMR
(300 MHz, (D6)DMSO): 6.59 (br. s, H2NꢀC(4)); 5.77 (br. s, H2NꢀC(2)); 4.78 (s, 2 HꢀC(6)); 4.05 (br. t,
J ¼ 5.4, 2 HꢀC(8)); 3.92 (br. t, J ¼ 5.1, 2 HꢀC(9)). 13C-NMR (75 MHz, (D6)DMSO): 159.04 (s, C(4));
154.76 (s, C(2)); 151.15 (s, C(10a)); 141.69 (s, C(5a)); 109.95 (s, C(4a)); 78.63 (t, C(6)); 64.23 (t, C(8));
63.17 (t, C(9)). HR-MALDI-MS: 207.0993 (100, [M þ H]þ, C8H11N6Oþ; calc. 207.0994).
Ethyl 2,6-Diamino-9-(2-ethoxy-2-oxoethyl)-9H-purine-8-carboxylate (31). Yield: 96%. Rf (CH2Cl2/
MeOH 5 :1) 0.51. M.p. 2248. IR (ATR): 3421m, 3300m, 3180s, 2923s, 2853w, 1714s, 1645m, 1628m, 1590s,
1469s, 1435m, 1422s, 1391s, 1369m, 1331m, 1294m, 1254s, 1208s, 1122w, 1071m, 1036s, 1016w, 981w, 936w,
1
905m, 870w, 828w, 790s, 775m. H-NMR (300 MHz, (D6)DMSO): 6.24 (br. s, H2NꢀC(6)); 5.64 (br. s,
H2NꢀC(2)); 5.04 (s, NCH2); 4.29, 4.15 (2q, J ¼ 7.1, 2 OCH2Me); 1.29, 1.20 (2t, J ¼ 7.2, 2 OCH2Me).
13C-NMR (75 MHz, (D6)DMSO): 167.47, 161.41 (2s, 2 C¼O); 158.54 (s, C(6)); 156.96 (s, C(2)); 152.57 (s,
C(4)); 133.85 (s, C(8)); 113.01 (s, C(5)); 61.61, 61.13 (2t, 2 OCH2Me); 44.55 (t, NCH2); 14.12 (q,
2 OCH2Me). HR-MALDI-MS: 309.1309 (100, [M þ H]þ, C12H17N6O4þ ; calc. 309.1311).
7,8-Dihydro-6-phenyl-6H-imidazo[1,2-e]purine-2,4-diamine (32). Yield: 94%. Rf (CH2Cl2/MeOH
5 :1) 0.70. M.p. 1968. IR (ATR): 3313m, 3161s, 1614m, 1592s, 1506s, 1456w, 1409s, 1330s, 1249m, 1136w,
1019m, 955w, 883w, 782m. 1H-NMR (300 MHz, (D6)DMSO): 7.75 (d, J ¼ 7.8, HꢀC(2’), HꢀC(6’)); 7.36 (t,
J ¼ 7.2, HꢀC(3’), HꢀC(5’)); 6.96 (t, J ¼ 7.2, HꢀC(4’)); 6.20 (br. s, H2NꢀC(4)); 5.59 (br. s, H2NꢀC(2)); 4.46,
4.19 (2dd, J ¼ 9.6, 6.3, 2 HꢀC(7), 2 HꢀC(8)). 13C-NMR (75 MHz, (D6)DMSO): 158.28 (s, C(4)); 152.96
(s, C(2)); 150.37 (s, C(9a)); 149.14 (s, C(1’)); 139.88 (s, C(5a)); 128.28 (d, C(3’), C(5’)); 120.02 (d, C(4’));

Helvetica Chimica Acta – Vol. 94 (2011)
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114.43 (d, C(2’), C(6’)); 111.71 (s, C(4a)); 50.44, 48.53 (2t, C(7), C(8)). HR-MALDI-MS: 268.1198 (100,
[M þ H]þ, C13H14Nþ7 ; calc. 268.1311).
Diethyl 1,1’-(2-Amino-5-nitrosopyrimidine-4,6-diyl)dipiperidine-4-carboxylate (37). A suspension of
2-amino-4,6-dimethoxy-5-nitrosopyrimidine (33; 250 mg, 1.36 mmol) in EtOH (3 ml) was treated with
ethyl isonipecotate (412 ml, 2.72 mmol) and stirred at r.t. for 2 h until TLC and LC/MS showed
disappearance of the starting material. After evaporation, the residue was suspended in Et2O. The
precipitate was filtered off, washed with Et2O, and dried under vacuum to afford 37 (512 mg, 85%). Dark
violet powder. Rf (CH2Cl2/MeOH 9 :1) 0.43. M.p. 988. IR (ATR): 3325w, 3186w, 2936m, 2865w, 1722s,
1628m, 1556w, 1511s, 1442s, 1373m, 1316s, 1271s, 1202s, 1154s, 1109w, 1095w, 1034s, 995s, 936m, 889w,
859m, 832w, 797m, 766m. 1H-NMR (300 MHz, (D6)DMSO): 7.93 (br. s, H2NꢀC(2)); 4.08 (q, J ¼ 7.2,
2 OCH2Me); 2.98 (br. t, J ¼ 9.9, 4 HꢀC(2’), 4 HꢀC(6’)); 2.76 – 2.65 (m, 2 HꢀC(4’)); 1.97 – 1.17 (m,
4 HꢀC(3’), 4 HꢀC(5’)); 1.14 (t, J ¼ 7.2, 2 OCH2Me). 13C-NMR (75 MHz, (D6)DMSO): 173.35 (s,
2 C¼O); 165.00 (s, C(2)); 161.63, 150.28 (2s, C(4), C(6)); 140.15 (s, C(5)); 59.89 (t, 2 OCH2Me); 49.88 (t,
2 C(2’), 2 C(6’)); 42.81 (t, 2 C(4’)); 27.67 (t, 2 C(3’), 2 C(5’)); 14.67 (q, 2 OCH2Me). HR-MALDI-MS:
435.2350 (100, [M þ H]þ, C20H31N6O5þ ; calc. 435.2356), 417.2244 (13, [M ꢀ OH]þ, C20H29N6Oþ4 ; calc.
417.2250), 404.2289 (43, [M ꢀ NO]þ, C20H30N5O4þ ; calc. 404.2298).
General Procedure for the Denitrosation of the 4,6-Bis(dialkylamino)-5-nitrosopyrimidines 34 – 37
(GP 3). A suspension of the nitroso amines 34 – 37 in Ph2O (1 ml) was heated to 2108. Progress of the
reaction was monitored by LC/MS. After a few min of heating, a new peak corresponding to the loss of
the NO group was formed in all cases. Upon continued heating, LC/MS analysis showed the progressive
disappearance of starting material, and, as based on the mass, formation of denitrosated products.
Purification by flash column chromatography (pentane for removal of Ph2O, then MeCN/EtOH 1:2 to
1:1) gave 38 – 41.
4,6-Di(morpholin-4-yl)pyrimidin-2-amine (40). Morpholine (135 ml, 1.53 mmol) was added dropwise
at r.t. to a suspension of NaH (60% dispersion in oil, 58 mg, 1.52 mmol) in DMSO (5 ml), and the mixture
was stirred for 15 min. 2-Amino-4,6-dichloropyrimidine (100 mg, 0.61 mmol) was added, and the mixture
was heated at 808 for 3 h. Progress of the reaction was monitored by LC/MS. After 40 min, LC/MS
showed two peaks, corresponding to starting material and to the product of monosubstitution. Heating
was continued until consumption of starting material. After cooling, MeOH was added, morpholine was
removed in vacuo, and the residue was extracted with CH2Cl2. Evaporation of the solvent and
purification by flash column chromatography (CH2Cl2) provided 40 (113 mg, 70%). Rf (CH2Cl2/
1
MeOH 9 :1) 0.60. H-NMR (300 MHz, CDCl3): 5.13 (s, HꢀC(5)); 4.50 (br. s, H2NꢀC(2)); 3.73 (br. s,
4 HꢀC(2’), 4 HꢀC(6’)); 3.48 (br. s, 4 HꢀC(3’), 4 HꢀC(5’)). 13C-NMR (75 MHz, CDCl3): 163.99 (2s, C(4),
C(6)); 161.61 (s, C(2)); 73.13 (s, C(5)); 65.85 (2t, 2 C(2’), 2 C(6’)); 44.25 (2t, 2 C(3’), 2 C(5’)).
Diethyl 1,1’-(2-Aminopyrimidine-4,6-diyl)dipiperidine-4-carboxylate (41). Prepared according to
GP 3 (15 min at 2108). Yield: 75%. Rf (CH2Cl2/MeOH 9 :1) 0.64. 1H-NMR (300 MHz, CDCl3): 5.60 (br.
s, H2NꢀC(2)); 5.20 (s, HꢀC(5)); 3.74 (q, J ¼ 7.1, 2 OCH2Me); 2.92 (br. t, J ¼ 11.1, 4 HꢀC(2’), 4 HꢀC(6’));
2.65 – 2.46 (m, 4 HꢀC(3’), 4 HꢀC(5’)); 1.15 (t, J ¼ 7.1, 2 OCH2Me). 13C-NMR (75 MHz, CDCl3): 174.63
(s, 2 C¼O); 164.24 (s, C(2)); 160.80 (2s, C(4), C(6)); 74.10 (s, C(5)); 60.74 (t, 2 OCH2Me)); 44.02, 41.40
(2t, 2 C(2’), 2 C(6’)); 29.70, 27.70 (2t, 2 C(3’), 2 C(5’)); 14.22 (q, 2 OCH2Me).
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Received March 7, 2011