Synthesis of 4-aminopyrazolo[3,4-d]pyrimidine derivatives from 5-acetyl-6-amino-4-methylsulfanyl- or 5-acetyl-6-amino-4- methylsulfonylpyrimidines

Article abstract of DOI:10.1007/s11172-012-0046-1

Diacetyl ketene N,S-acetal was used for the synthesis of 5-acetyl-6-amino-4-methylsulfanylpyrimidines substituted at the exocyclic nitrogen atom, which were further oxidized with m-chloroperbenzoic acid to the corresponding methylsulfonylpyrimidines. Reac

Full text of DOI:10.1007/s11172-012-0046-1

Russian Chemical Bulletin, International Edition, Vol. 61, No. 2, pp. 332—342, February, 2012
332
Synthesis of 4ꢀaminopyrazolo[3,4ꢀd]pyrimidine derivatives
from 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfanylꢀ
or 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfonylpyrimidines
A. V. Komkov, V. A. Voronkova, A. S. Shashkov, and V. A. Dorokhov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: vador@ioc.ac.ru
Diacetyl ketene N,Sꢀacetal was used for the synthesis of 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylꢀ
sulfanylpyrimidines substituted at the exocyclic nitrogen atom, which were further oxidized
with mꢀchloroperbenzoic acid to the corresponding methylsulfonylpyrimidines. Reactions of
hydrazines with these pyrimidines containing vicinal Ac and MeS (or MeSO2) groups were used
for the preparation of new 4ꢀaminopyrazolo[3,4ꢀd]pyrimidine derivatives.
Key words: 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfanylpyrimidines, oxidation, mꢀchloroperbenzoic
acid, 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfonylpyrimidines, 4ꢀaminoꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidꢀ
ines, 4ꢀaminoꢀ2ꢀphenylꢀ2Hꢀpyrazolo[3,4ꢀd]pyrimidines, hydrazines.
Earlier,20 we have shown that Nꢀbenzoylaminal 1
reacts with benzoyl isothiocyanate as a Cꢀnucleophile
to form benzoylthioamide 2, which is easily converted to
5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfanylꢀ2ꢀphenylpyrimidine (3)
(Scheme 1).
Pyrazolo[3,4ꢀd]pyrimidines are of great biological imꢀ
portance since they are purine analogs and antagonists. In
the last 10—15 years, 4ꢀamino derivatives of this heteroꢀ
cyclic system are of special interest, which is due to their
activity as inhibitors of tyrosineꢀ1,2 and serineꢀthreonine
proteinkinases,3 as well as of a number of other enzymes,4—10
thus making them potentially promising antitumor, antiꢀ
viral, and antibacterial agents.
4ꢀAminopyrazolo[3,4ꢀd]pyrimidines commonly are
obtained by annulation of a pyrimidine ring to the correꢀ
sponding substituted pyrazoles (see, for example, the reꢀ
view11 and the works2,5,10,12—16) or by the action of hydrꢀ
azines on aminopyrimidines containing vicinal functional
groups at positions 4 and 5 (Cl and CHO (see Refs 3, 7, 8,
and 17); Cl and CN (see Ref. 18); MeS and CN (see
Ref. 19)).
In the present work, we synthesized a number of subꢀ
stituted at the exocyclic nitrogen atom pyrimidines 4a—i
from diacetyl ketene N,Sꢀacetal 5 following Scheme 2,
which includes formation of ketene aminals 6, deacetylaꢀ
tion of the latter to aminals 7 and preparation of thioꢀ
amides 8 with their subsequent cyclization to pyrimidineꢀ
thiones 9 (compounds 9a and 9h were synthesized earlier21).
Readily occurring alkylation of pyrimidinethiones 9a—i
with MeI gives new methylsulfanylpyrimidines 4a—i.
We found that prolonged reflux in butanol of pyrimꢀ
idines 4a—d with a large excess of hydrazine hydrate or
methylhydrazine (a 25ꢀfold excess of hydrazine hydrate in
the case of pyrimidines 4a—c and a 50ꢀfold excess in the
case of compound 4d and when methylhydrazine was used)
gives rise to the substituted 4ꢀaminopyrazolo[3,4ꢀd]ꢀ
In the present work, we report the use of 5ꢀacetylꢀ6ꢀ
aminoꢀ4ꢀmethylsulfanylpyrimidines and 5ꢀacetylꢀ6ꢀaminoꢀ
4ꢀmethylsulfonylpyrimidines for the preparation of new
4ꢀaminopyrazolo[3,4ꢀd]pyrimidine derivatives.
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 330—340, February, 2012.
1066ꢀ5285/12/6102ꢀ332 © 2012 Springer Science+Business Media, Inc.

4ꢀAminopyrazolo[3,4ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
333
Scheme 2
R1R2N =
R1 = H, R2 = 3,5ꢀMe2C6H3 (e), 3ꢀClC6H4 (f), 3ꢀCF3C6H4 (g), PhCH2 (h), C4H9 (i)
(a),
(b),
(c),
(d),
Reagents and conditions: i. R1R2NH, C6H6 or oꢀxylene, or THF for 6a, ; ii. MeONa, MeOH, 20 C or ; iii. PhCONCS, C6H6 or
toluene, 20 C; iv. 1) MeONa, MeOH, , 2) AcOH, 20 C; v. 1) MeONa, MeOH, 20 C, 2) MeI, 20 C.
pyrimidines 10a—d and 11a—c with good yields (only
compound 11d was isolated in low yield since a consiꢀ
derable amount of the starting pyrimidine 4d accordꢀ
ing to the TLC data was not involved into the reaction,
Scheme 3).
glets for the MeS and Me groups of both reaction products
at  ~2.7 and 2.2; Scheme 4).
Scheme 4
Scheme 3
R3 = H (10), Me (11); R1R2N =
(c),
(a),
(b),
(d)
R1 = H; R2 = H (3, 12a, 13a), 3,5ꢀMe2C6H3 (4e, 12b, 13b)
However, it turned out that when conditions for the
synthesis of compounds 10a—d and 11a—d were applied
to 4ꢀmethylsulfanylpyrimidines 3, 4e and hydrazine hyꢀ
drate, no target pyrazolo[3,4ꢀd]pyrimidines were obtained,
with the mixtures of hydrazones 12a,b and azines 13a,b
being formed instead in the molar ratio ~2 : 1 and 8 : 1,
respectively (the 1H NMR spectra of which exhibited sinꢀ
It could have been suggested that the annulation of the
pyrazole ring would occur more readily if the methylsulfaꢀ
nyl group is oxidized to a methylsulfonyl one. In this conꢀ
nection, treatment of sulfanylpyrimidines 3 and 4e—i with
a 2.5ꢀfold excess of 40% MCPBA in chloroform afforded

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Komkov et al.
Scheme 5
R1 = H; R2 = H (3, 14a, 15a), 3,5ꢀMe2C6H3 (4e, 14b, 15b), 3ꢀClC6H4 (4f, 14c, 15c), 3ꢀCF3C6H4 (4g, 14d, 15d), PhCH2 (4h, 14e, 15e),
C4H9 (4i, 14f, 15f)
Scheme 6
5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfonylpyrimidines 14a—f in
24—56% yields (Scheme 5). It was found that the moderꢀ
ate yields of compounds 14a—f can be accounted for by
the formation of side oxidation products, i.e., 5ꢀacetoxyꢀ
6ꢀaminoꢀ4ꢀmethylsulfonylpyrimidines 15a—f (a type of
the Baeyer—Villiger rearrangement). The target comꢀ
pounds 14 should be purified from the side products by
column chromatography on silica gel. The 1H NMR specꢀ
tra showed that before chromatographic purification the
content of 5ꢀacetoxypyrimidines 15d,e,f in the reaction
mixtures was 17, 43, and 60%, respectively. Pyrimidines
15e,f were isolated in the pure form, though, silica gel
seems to cause partial decomposition of these compounds.
The structure of methylsulfonylpyrimidines 14a—f was
confirmed by spectroscopic data. Their mass spectra (EI)
exhibit strong peaks of molecular ions, whereas in the
1H NMR spectra (CDCl3) the signal for the MeSO2 is
observed more downfield (for example, for 14e at  3.39)
than the signal for the MeS in the starting methylsulfaꢀ
nylpyrimidines. The presence of the acetyl group is indiꢀ
cated by the signal in the 13C NMR spectrum (for 14e at
 201.54). In the 13C NMR spectrum (CDCl3) of acetoxyꢀ
pyrimidine 15e, the signal for the carbonyl carbon atom
was found in much higher field at  168.50. In the high
resolution mass spectrum (ESI) of compound 15e, the
peak [M + Na]+was observed in the positive range and
[M – H]– in the negative range.
R3 = H (10), Me (11); R1 = R2 = H (14a, 10e, 11e), R1 = H, R2
=
= 3,5ꢀMe2C6H3 (14b, 10f, 11f); R1 = H, R2 = 3ꢀClC6H4 (14c, 10g);
R
1 = H, R2 = 3ꢀCF3C6H4 (14d, 10h); R1 = H, R2 = PhCH2 (14e, 10i)
C(7a), whereas no correlation is observed between the
NMe protons and the carbon atom C(3), which, in turn,
correlates with the protons of the Me group. In the 2D
1H/15N HMBC spectrum of compound 11f, the more upꢀ
field nitrogen atom N(1) (–200) correlates only with the
NMe protons, whereas for the more downfield nitrogen
atom N(2) (–72) the correlation is observed with both the
NMe protons and the Me protons. In the 2D 1H/15N
HMBC spectrum of compound 10i, a correlation of the
protons of the Me group with the nitrogen atom at  –85 is
observed (the chemical shift in the low field indicates that
the atom N(2) is attached to a double bond, and, thereꢀ
fore, the proton is attached to the atom N(1)).
The synthesized 4ꢀmethylsulfonylpyrimidines 14a—e
smoothly react with hydrazine hydrate and methylhydrꢀ
azine upon reflux in butanol to form 4ꢀaminopyrazoloꢀ
[3,4ꢀd]pyrimidines 10e—i and 11e,f, isolated as colorless
crystals in good yields (Scheme 6).
Reflux of 4ꢀmethylsulfonylpyrimidines 14b,f with exꢀ
cess phenylhydrazine in butanol gives rise to 4ꢀaminoꢀ2ꢀ
phenylꢀ2Hꢀpyrazolo[3,4ꢀd]pyrimidines 16a,b, which were
isolated only in 29% yield (Scheme 7).
The structure of the synthesized pyrazolopyrimidines
was confirmed by spectroscopic methods. Thus, there are
strong peaks of molecular ions in the mass spectra (EI) of
compounds 10a,e—i and 11a,e,f, whereas heterocycles
10b—d and 11b—d have very weak molecular ion peaks
since electron impact induces successive cleavage of the
piperazine ring. Position of the Me group in biheterocyꢀ
cles 11 and of the proton in pyrazolopyrimidines 10 at the
atom N(1) was confirmed by 2D NMR spectra. Thus, in
the 2D 1H/13C HMBC spectra of compounds 11a,e,f, the
protons of the NMe group correlate with the carbon atom
The structure of compounds 16a,b was confirmed by
spectroscopic data. The mass spectrum (EI) of compound
16a exhibits a strong peak of molecular ion, whereas in the
high resolution mass spectrum (ESI) of pyrazolopyrimiꢀ
dine 16b, the [M + H]+ and [M + Na]+ peaks are obꢀ
served. The position of the Ph group at the atom N(2) was
established based on the 1H NOE spectra, 2D 1H/1H
1
gNOESY and H/15N HMBC spectra and confirmed by
comparison of the 13C NMR spectra of these compounds
with those of 1Hꢀpyrazolo[3,4ꢀd]pyrimidines 10 and 11.
In the selective 1D spectrum of compound 16b (CDCl3),

4ꢀAminopyrazolo[3,4ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
335
Scheme 7
R1 = H; R2 = 3,5ꢀMe2C6H3 (14b, 16a), Bun = (14f, 16b)
a sprayer gas (4 L min–1), the interface temperature was 180 C.
The following reactants were used in the synthesis: anilines,
piperazines, and MCPBA from Lancaster and Acros, benzoyl
isothiocyanate from Fluka; anhydrous benzene and toluene were
obtained by distillation over Na; methanol was fractionally disꢀ
tilled before use. Column chromatography was carried out
on Merck Silicagel 60 (0.063—0.200 mm). Diacetyl ketene
N,Sꢀacetal 5 (m.p. 118—119 C) was obtained according to the
known procedure;22 5ꢀacetylꢀ6ꢀmorpholinoꢀ2ꢀphenylpyrimidꢀ
ineꢀ4(3H)ꢀthione (9a) (m.p. 209—210 C) and 5ꢀacetylꢀ6ꢀamiꢀ
noꢀ4ꢀmethylsulfanylꢀ2ꢀphenylpyrimidine (3) (m.p. 152—153 C)
were obtained according to the procedures described earlier.20,21
3ꢀ[Amino(4ꢀmethylpiperazinꢀ1ꢀyl)methylidene]pentaneꢀ2,4ꢀ
dione (6b). A mixture of N,Sꢀketene acetal 5 (1.45 g, 8.3 mmol)
and Nꢀmethylpiperazine (1.01 mL, 9.1 mmol) in benzene
(18 mL) was refluxed for 1 h, cooled to ~20 C, a precipitate was
filtered off, washed with benzene (5 mL) and light petroleum
(10 mL) to obtain ketene aminal 6b (0.83 g, 44%), m.p. 248—249 C.
Found (%): C, 58.71; H, 8.54; N, 18.40. C11H19N3O2. Calculatꢀ
a positive NOE is observed for the orthoꢀprotons PhN
(2.0%) at  7.51 and the proton NH (2.2%) at  5.33 when
the protons of the Me group at  2.68 are irradiated, whereꢀ
as in the 2D 1H/1H gNOESY spectrum of compound 16a,
a correlation peak is observed for the methyl protons and
the orthoꢀprotons of PhN. The 2D 1H/15N HMBC specꢀ
tra of compounds 16a,b exhibit correlation peaks for the
atom N(2) and the methyl protons, as well as the orthoꢀ
protons of PhN. In the 13C NMR spectra, the signal for
the carbon atom C(3) in 2Hꢀpyrazolopyrimidines 16 is
found in the higher field as compared to 1Hꢀpyrazoloꢀ
pyrimidines 10 and 11. On the contrary, the signal for the
carbon atom C(7a) was found in the lower field ( 132.45
(C(3)),  160.44 (C(7a)) for compound 16a;  140.64
(C(3)),  157.26 (C(7a)) for pyrazolopyrimidine 10f;
 138.89 (C(3)),  155.87 (C(7a)) for heterocycle 11f).
In conclusion, for the first time we have shown that
pyrazolo[3,4ꢀd]pyrimidines can be successfully synthesized
from pyrimidines with vicinal acetyl and methylsulfonyl
groups as the starting compounds.
1
ed (%): C, 58.64; H, 8.50; N, 18.65. H NMR (DMSOꢀd6), :
1.98 (s, 6 H, 2 MeCO); 2.20 (s, 3 H, NMe); 2.38 (m, 4 H,
2 CH2N); 3.49 (m, 4 H, 2 CH2N); 8.12 (br.s, 1 H, NH); 8.49
(br.s, 1 H, NH).
3ꢀ{Amino[4ꢀ(4ꢀmethoxyphenyl)piperazinꢀ1ꢀyl]methylidene}ꢀ
pentaneꢀ2,4ꢀdione (6c) was synthesized similarly to ketene aminal
6b from N,Sꢀacetal 5 and Nꢀ(4ꢀmethoxyphenyl)piperazine. The
reaction time was 3 h, the yield was 41%, m.p. 231—232 C.
Found (%): C, 64.11; H, 7.27; N, 13.30. C17H23N3O3. Calculatꢀ
Experimental
1
H NMR spectra were recorded on a Bruker AMꢀ300
1
1
spectrometer (300 MHz), 13C NMR, H NOE, 2D H/13C and
1H/15N HMBC, and 1H/1H gNOESY spectra were recorded on
a Bruker Avance 600 spectrometer (600, 150, and 60.8 MHz for
1H, 13C, and 15N, respectively). Residual signals of the deuteratꢀ
ed solvent ( 7.27 for CDCl3 and  2.50 for DMSOꢀd6) were used
1
ed (%): C, 64.33; H, 7.30; N, 13.24. H NMR (DMSOꢀd6), :
1.98 (s, 6 H, 2 MeCO); 3.08 (m, 4 H, 2 CH2N); 3.61 (m, 4 H,
2 CH2N); 3.68 (s, 3 H, OMe); 6.81 (d, 2 H, C6H4, J = 7.5 Hz);
6.92 (d, 2 H, C6H4, J = 7.5 Hz); 8.21 (br.s, 1 H, NH); 8.52 (br.s,
1 H, NH).
1
as a reference in the H NMR spectra. Multiplet signals of the
deuterated solvent ( 39.50 for DMSOꢀd6 and  77.00 for CDCl3)
were the reference in the 13C NMR spectra. 15N chemical shifts
were measured using MeNO2 as an external standard (highꢀfield
chemical shifts are given as the negative values). IR spectra were
recorded on a SpecordꢀM82 spectrometer and mass spectra were
recorded on a Kratos MSꢀ30 instrument (EI, 70 eV, the temperꢀ
ature of the injection chamber was 250 C, direct injection).
High resolution mass spectra were recorded on a Bruker miꢀ
crOTOF II instrument (ESI). Measurements were carried out in
the positive and the negative ranges (capillary voltage was 4500 V).
The masses were scanned in the range m/z 50 — 3000 Da using
an external and an internal calibration (Electrospray Calibrant
Solution, Fluka). An acetonitrile solution of a compound was
injected by a syringe, the flow rate was 3 m min–1, nitrogen was
3ꢀ{Amino[4ꢀ(4ꢀfluorophenyl)piperazinꢀ1ꢀyl]methylidene}ꢀ
pentaneꢀ2,4ꢀdione (6d) was synthesized similarly to ketene
aminal 6b from N,Sꢀacetal 5 and Nꢀ(4ꢀfluorophenyl)piperazine.
The reaction time was 3 h, the yield was 45%, m.p. 235—236 C.
Found (%): C, 62.88; H, 6.77; N, 13.75. C16H20FN3O2. Calcuꢀ
lated (%): C, 62.93; H, 6.60; N, 13.76. 1H NMR (DMSOꢀd6), :
1.99 (s, 6 H, 2 MeCO); 3.15 (m, 4 H, 2 CH2N); 3.62 (m, 4 H,
2 CH2N); 6.95 (m, 2 H, C6H4); 7.04 (m, 2 H, C6H4); 8.21 (br.s,
1 H, NH); 8.56 (br.s, 1 H, NH).
Pyrimidineꢀ4(3H)ꢀthiones (9b—d). A mixture of the corꢀ
responding ketene aminal 6b—d (3.5 mmol) and MeONa
(4.2 mmol) in MeOH (6 mL) was refluxed for 4 h, cooled to ~20 C,
followed by addition of glacial AcOH (0.24 mL, 4.2 mmol).
After evaporation of the solvent in vacuo, CHCl3 (15 mL) was

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Komkov et al.
added to the residue, AcONa was filtered off, the filtrate was
concentrated in vacuo, PhCONCS (0.70 mL, 5.2 mmol) in toluꢀ
ene (8 mL) was added to the residue (oil) and the mixture was
allowed to stand at 20 C for 10 h. A precipitate formed was
filtered off and washed with light petroleum (20 mL), followed
by addition of MeONa (3.5 mmol) in MeOH (9 mL) and reflux
for 5 min (until entire dissolution). Then, the mixture was cooled
to 20 C, acidified with AcOH, a precipitate formed was filtered
off, washed with MeOH (3 mL) to obtain 5ꢀacetylꢀ6ꢀ(4ꢀmethylꢀ
piperazinꢀ1ꢀyl)ꢀ2ꢀphenylpyrimidineꢀ4(3H)ꢀthione (9b), 5ꢀacetylꢀ
6ꢀ[4ꢀ(4ꢀmethoxyphenyl)piperazinꢀ1ꢀyl]ꢀ2ꢀphenylpyrimidineꢀ
4(3H)ꢀthione (9c), and 5ꢀacetylꢀ6ꢀ[4ꢀ(4ꢀfluorophenyl)piperazinꢀ
1ꢀyl]ꢀ2ꢀphenylpyrimidineꢀ4(3H)ꢀthione (9d) as yellow crystals.
The yields, melting points, and elemental analysis data are given
in Table 1, the 1H NMR spectra, in Table 2.
Pyrimidineꢀ4(3H)ꢀthiones (9e—i). A mixture of N,Sꢀketene
acetal 5 (1.0 g, 5.8 mmol) and the corresponding amine (6.3 mmol)
in oꢀxylene (10 mL) (in the case of arylamines) or in benzene
(10 mL) (in the case of alkylamines) was refluxed for 4 h, the solvent
was evaporated in vacuo, MeONa (5.8 mmol) in MeOH (8 mL)
was added to the residue (oil) and the mixture was allowed to
stand at 20 C for 3—6 h (TLC monitoring). Then, glacial AcOH
(0.33 mL, 5.8 mmol) was added, the solvent was evaporated
in vacuo, benzene (15 mL) was added to the residue, AcONa was
filtered off, the filtrate was concentrated in vacuo, PhCONCS
(1.17 mL, 8.7 mmol) in benzene (10 mL) was added to the resiꢀ
due (oil) and the mixture was allowed to stand at 20 C for 3 h.
Then, light petroleum (20 mL) was added, the solvent was deꢀ
canted, MeONa (5.8 mmol) in MeOH (6 mL) was added to the
oil obtained, heated to boiling point, cooled to 20 C, and acidiꢀ
fied with AcOH. A precipitate formed was filtered off and washed
with MeOH (4 mL) to obtain 5ꢀacetylꢀ6ꢀ(3,5ꢀdimethylphenylꢀ
amino)ꢀ2ꢀphenylpyrimidineꢀ4(3H)ꢀthione (9e), 5ꢀacetylꢀ6ꢀ(3ꢀ
chlorophenylamino)ꢀ2ꢀphenylpyrimidineꢀ4(3H)ꢀthione (9f),
5ꢀacetylꢀ2ꢀphenylꢀ6ꢀ(3ꢀtrifluoromethylphenylamino)pyrimidꢀ
ineꢀ4(3H)ꢀthione (9g), 5ꢀacetylꢀ6ꢀbenzylaminoꢀ2ꢀphenylpyriꢀ
midineꢀ4(3H)ꢀthione (9h), and 5ꢀacetylꢀ6ꢀbutylaminoꢀ2ꢀpheꢀ
nylpyrimidineꢀ4(3H)ꢀthione (9i) as yellow crystals. The yields,
melting points, and elemental analysis data are given in Table 1,
the 1H NMR spectra, in Table 2.
4ꢀMethylsulfanylpyrimidines (4a, c—i). Sodium methoxide
(5.3 mmol) in MeOH (12 mL) was added to the corresponding
pyrimidinethione 9a,c—i (3.5 mmol) and the mixture was stirred
for 10 min at 20 C until complete dissolution, then MeI
(0.65 mL, 10.5 mmol) was added and this was allowed to stand at
20 C for 30 min. A precipitate formed was filtered off to obtain
5ꢀacetylꢀ4ꢀmethylsulfanylꢀ6ꢀmorpholinoꢀ2ꢀphenylpyrimidꢀ
ine (4a), 5ꢀacetylꢀ4ꢀmethylsulfanylꢀ6ꢀ[4ꢀ(4ꢀmethoxyphenyl)ꢀ
piperazinꢀ1ꢀyl]ꢀ2ꢀphenylpyrimidine (4c), 5ꢀacetylꢀ6ꢀ[4ꢀ(4ꢀ
fluorophenyl)piperazinꢀ1ꢀyl]ꢀ4ꢀmethylsulfanylꢀ2ꢀphenylpyrimꢀ
idine (4d), 5ꢀacetylꢀ4ꢀmethylsulfanylꢀ6ꢀ(3,5ꢀdimethylphenylꢀ
amino)ꢀ2ꢀphenylpyrimidine (4e), 5ꢀacetylꢀ6ꢀ(3ꢀchlorophenylꢀ
amino)ꢀ4ꢀmethylsulfanylꢀ2ꢀphenylpyrimidine (4f), 5ꢀacetylꢀ
4ꢀmethylsulfanylꢀ2ꢀphenylꢀ6ꢀ(3ꢀtrifluoromethylphenylamino)ꢀ
pyrimidine (4g), 5ꢀacetylꢀ6ꢀbenzylaminoꢀ4ꢀmethylsulfanylꢀ2ꢀ
phenylpyrimidine (4h), and 5ꢀacetylꢀ6ꢀbutylaminoꢀ4ꢀmethylꢀ
sulfanylꢀ2ꢀphenylpyrimidine (4i) as colorless or pale yellow
crystals. Analytically pure samples were obtained by recrystalꢀ
lization from hexane. The yields, melting points, and elemenꢀ
tal analysis data are given in Table 1, the 1H NMR spectra,
in Table 2.
5ꢀAcetylꢀ6ꢀ(4ꢀmethylpiperazinꢀ1ꢀyl)ꢀ4ꢀmethylsulfanylꢀ2ꢀ
phenylpyrimidine (4b). Sodium methoxide (2.25 mmol) in MeOH
(5 mL) was added to pyrimidinethione 9b (0.50 g, 1.5 mmol) and
left to stand at 20 C for 10 min until complete dissolution, then
MeI (0.28 mL, 4.5 mmol) was added and the mixture was alꢀ
lowed to stand at 20 C for 1 h. Methanol was evaporated in vacuo,
benzene (15 mL) was added to the residue, NaI was filtered off,
benzene was evaporated in vacuo, the residue was crystallized
with light petroleum (3 mL) to obtained pyrimidine 4b (0.27 g,
52%) (see Tables 1 and 2).
Pyrazolo[3,4ꢀd]pyrimidines (10a—d). A mixture of the corꢀ
responding pyrimidine 4a—d (0.4 mmol) and hydrazine hydrate
(0.5 mL, 10 mmol in the case of 4a—c or 1.0 mL, 20 mmol in the
case of 4d) in BuOH (5 mL) was refluxed for 7—10 h (disappearꢀ
ance of the starting pyrimidines 4 was monitor by TLC). The
solvent and excess hydrazine were evaporated in vacuo, the resiꢀ
due was washed with diethyl ether (5 mL) to obtain compounds
10a—d as colorless crystals. Analytically pure samples were isoꢀ
lated by recrystallization from acetonitrile. The yields, melting
points, and elemental analysis data are given in Table 3, the
1H NMR spectra, in Table 4.
3ꢀMethylꢀ4ꢀmorpholinoꢀ6ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrꢀ
imidine (10a). MS, m/z (Irel (%)): 295 [M]+ (72), 265 [M – CH2O]+
(34), 250 [M – CH2OCH3]+ (43), 238 [M – CH2OCH2CH]+
(93), 209 [M – (CH2)2O(CH2)2N]+ (58), 66 (100). IR (CHCl3),
/cm–1: 3456 (NH), 1584, 1552.
3ꢀMethylꢀ4ꢀ(4ꢀmethylpiperazinꢀ1ꢀyl)ꢀ6ꢀphenylꢀ1Hꢀpyrazoloꢀ
[3,4ꢀd]pyrimidine (10b). MS, m/z (Irel (%)): 308 [M]+ (8), 252
[M – MeNCH2CH]+ (19), 238 [M – MeN(CH)CH2CH2]+
(100), 209 [M – MeN(CH2)4N]+ (31). IR (CHCl3), /cm–1
:
3456 (NH), 1592 sh, 1580, 1552.
4ꢀ[4ꢀ(4ꢀMethoxyphenyl)piperazinꢀ1ꢀyl]ꢀ3ꢀmethylꢀ6ꢀphenylꢀ
1Hꢀpyrazolo[3,4ꢀd]pyrimidine (10c). MS, m/z (Irel (%)): 400 [M]+
(37), 251 [M – MeOC6H4NCH2CH2]+ (28), 238 [M – MeOꢀ
C6H4N(CH)CH2CH2]+ (100), 209 [M – MeOC6H4N(CH2)4N]+
(33). IR (CHCl3), /cm–1: 3460 (NH), 1580, 1552, 1512.
4ꢀ[4ꢀ(4ꢀFluorophenyl)piperazinꢀ1ꢀyl]ꢀ3ꢀmethylꢀ6ꢀphenylꢀ
1Hꢀpyrazolo[3,4ꢀd]pyrimidine (10d). MS, m/z (Irel (%)): 388 [M]+
(6), 251 [M – FC6H4NCH2CH2]+ (55), 238 [M – FC6H4Nꢀ
(CH)CH2CH2]+ (100), 210 [M – FC6H4N(CH2)3CHN]+ (52),
209 [M – FC6H4N(CH2)4N]+ (47). IR (CHCl3), /cm–1: 3460
(NH), 1580, 1552, 1512.
1ꢀMethylpyrazolo[3,4ꢀd]pyrimidines (11a—d). A mixture of
the corresponding pyrimidine 4a—d (0.75 mmol) and methylꢀ
hydrazine (2.0 mL, 37.5 mmol) in BuOH (5 mL) was refluxed
for 14 h. In the synthesis of compounds 11a,b,d, the solvent and
excess hydrazine were evaporated in vacuo, the residue was subꢀ
jected to column chromatography on SiO2 (eluent: chloroform,
then chloroform—MeOH 50 : 0.2, 50 : 0.5, 50 : 1). The solvent
from the corresponding fractions was evaporated in vacuo, the
residue was washed with light petroleum (2 mL) to obtain comꢀ
pounds 11a,b,d as colorless crystals. In the preparation of comꢀ
pound 11c, the reaction mixture was cooled to 20 C, a precipiꢀ
tate formed was filtered off, washed with light petroleum (5 mL)
to obtain pyrazolopyrimidine 11c. Analytically pure samples of
compounds 11a—d were obtained by recrystallization from aceꢀ
tonitrile. The yields, melting points, and elemental analysis data
are given in Table 3, the 1H NMR spectra, in Table 4.
1,3ꢀDimethylꢀ4ꢀmorpholinoꢀ6ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrꢀ
imidine (11a). MS, m/z (Irel (%)): 309 [M]+ (100), 279 [M – CH2O]+
(30), 265 [M – CH2OCH2]+ (43), 252 [M – CH2OCH2CH]+

4ꢀAminopyrazolo[3,4ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
337
Table 1. Yields, melting points. and elemental analysis data for pyrimidinethiones 9b—i, methylsulfanylpyrimꢀ
idines 4a—i, and methylsulfonylpyrimidines 14a—f
Comꢀ
pound
Yield
(%)
M.p./C
Found
Calculated
Molecular
formula
(%)
N
С
H
S
4а
4b
84
105—106
101—102
133—134
140—141
118—119
113—114
114—115
137—138
80—81
61.87
61.98
62.88
63.13
66.54
66.33
65.09
65.38
69.08
69.39
61.56
61.70
59.25
59.54
68.56
68.74
64.57
64.73
62.13
62.17
65.41
65.69
64.56
64.68
68.67
68.74
60.58
60.75
58.43
58.60
0—
5.73
5.81
6.31
6.48
6.04
6.03
5.42
5.49
5.90
5.82
4.40
4.36
3.88
4.00
5.39
5.48
6.58
6.71
6.04
6.14
5.66
5.75
5.18
5.18
5.68
5.48
4.05
3.97
3.47
3.67
0—
12.92
12.76
16.02
16.36
12.60
12.89
13.32
13.26
11.37
11.56
11.25
11.36
10.17
10.42
11.95
12.03
13.21
13.32
16.93
17.06
13.39
13.32
13.79
13.72
12.08
12.03
11.65
11.81
10.54
10.79
0—
9.81
9.73
9.40
9.36
7.28
7.38
00—
С17H19N3O2S
С18H22N4OS
С24H26N4O2S
С23H23FN4OS
С21H21N3OS
С19H16ClN3OS
С20H16F3N3OS
С20H19N3OS
С17H21N3OS
С17H20N4OS
С23H24N4O2S
С22H21FN4OS
С20H19N3OS
С18H14ClN3OS
С19H14F3N3OS
00000—
52
4c
77
4d
85
4e
85
8.63
8.82
00—
4f
88
4g
94
00—
4h
4i
93
9.05
9.18
91
10.02
10.16
9.88
9.76
7.44
7.63
9b
9c
49*
64*
42*
23**
27**
22**
48**
31**
54
227—228
219—220
226—228
229—230
180—181
188—189
9d
9e
00—
9.08
9.18
00—
9f
9g
9h
9i
00—
0—
205—206
(Ref. 21: 205—206)
156—157
63.80
63.76
53.97
53.59
63.82
63.78
56.84
56.78
54.87
55.17
63.22
62.97
58.84
58.77
6.29
6.35
4.43
4.50
5.31
5.35
4.15
4.01
3.89
3.70
5.03
5.02
6.06
6.09
13.87
13.94
14.25
14.42
10.65
10.63
10.31
10.46
9.43
10.56
10.64
10.92
11.01
7.95
С16H19N3OS
С13H13N3O3S
С21H21N3O3S
С19H16ClN3O3S
С20H16F3N3O3S
С20H19N3O3S
С17H21N3O3S
14a
14b
14c
14d
14e
14f
189—190
232—233
206—207
188—189
189—190
122—123
40
8.11
00—
56
54
00—
9.65
44
10.74
11.02
11.90
12.10
8.33
8.41
9.15
9.23
24
* Yields are calculated based on ketene aminals 6b—d.
** Yields are calculated based on N,Sꢀketene acetal 5.
(86), 224 [M – CH2OCH2CHNCH2]+ (52). IR (CHCl3), /cm–1
:
(mꢀCPh); 128.34 (oꢀCPh); 130.21 (pꢀCPh); 138.25 (ipsoꢀCPh); 139.10
(C(3)); 156.95 (C(7a)); 160.18 (C(6)), 160.22 (C(4)). The signals
were assigned based on the 2D 1H/13C HMBC spectrum.
1568, 1552. 13C NMR (CDCl3), : 17.16 (Me); 33.41 (NMe);
48.87 (2 CH2N); 66.71 (2 CH2O); 100.38 (C(3a)); 128.20

338
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Komkov et al.
Table 2. The 1H NMR spectra of pyrimidinethiones 9b—i, methylsulfanylpyrimidines 4a—i, and methylsulfonylpyrimidines 14a—f
in CDCl3
Comꢀ
pound
(J/Hz)
4а
4b
4c
4d
4e*
4f
2.48 (s, 3 H, MеCO); 2.63 (s, 3 H, SMе); 3.64 (m, 4 H, 2 CН2N); 3.81 (m, 4 H, 2 СН2O); 7.50 (m, 3 H, Ph);
8.47 (m, 2 H, Ph)
2.32 (s, 3 H, NMе); 2.46 (s, 3 H, MеCO); 2.51 (m, 4 H, 2 СН2N); 2.64 (s, 3 H, SMе); 3.71 (m, 4 H, 2 СН2N);
7.49 (m, 3 H, Ph); 8.47 (m, 2 H, Ph)
2.52 (s, 3 H, MеCO); 2.68 (s, 3 H, SMе); 3.18 (m, 4 H, 2 СН2N); 3.78 (s, 3 H, OMe); 3.85 (m, 4 H, 2 СН2N);
6.88 (m, 4 H, C6H4); 7.50 (m, 3 H, Ph); 8.49 (m, 2 H, Ph)
2.50 (s, 3 H, MеCO); 2.65 (s, 3 H, SMе); 3.21 (m, 4 H, 2 СН2N); 3.82 (m, 4 H, 2 СН2N); 6.91 (m, 2 H, C6H4);
6.98 (m, 2 H, C6H4); 7.49 (m, 3 H, Ph); 8.48 (m, 2 H, Ph)
2.32 (s, 6 H, 2 Mе); 2.72 and 2.80 (both s, 6 H, СОMе and SMе); 6.81 (s, 1 H, рꢀHC H ); 7.45 (m, 5 H, mꢀHPh
,
6
3
pꢀHPh and oꢀHC H ); 8.48 (m, 2 H, оꢀHPh); 11.35 (br.s, 1 Н, NH)
6
3
2.78 and 2.87 (both s, 6 H, СОMе and SMе); 7.12 (d, 1 H, рꢀHC H , J = 7.8); 7.32 (t, 1 H, mꢀHC H , J = 7.8);
7.51 (m, 4 H, mꢀHPh, pꢀHPh and oꢀHC H ); 8.02 (s, 1 H, оꢀHC H6);48.48 (m, 2 H, оꢀHPh); 11.53 (br.s, 1 Н, NH)
6
4
4
6
4
4g
4h
4i
2.79 and 2.88 (both s, 6 H, СОMе and 6SMе); 7.41 (d, 1 H, рꢀHC H , J = 7.8); 7.49 (m, 4 H, mꢀHPh, pꢀHPh and mꢀHC H );
7.72 (d, 1 H, oꢀHC H , J = 7.8); 8.40 (s, 1 H, оꢀHC H ); 8.46 (m, 62 H, оꢀHPh); 11.63 (br.s, 1 Н, NH)
4
6
4
2.73 and 2.80 (both s, 6 H, СОMе and SMе); 4.90 6(d4, 2 H, CH2, J = 5.0); 7.25—7.54 (m, 8 H, 3 HPh and 5 HPhCH );
6
4
2
8.48 (m, 2 H, Ph); 9.88 (br.t, 1 Н, NH)
0.97 (t, 3 H, MеСН2, J = 7.2); 1.45 (m, 2 H, СН2); 1.68 (m, 2 H, СН2); 2.72 and 2.78 (both s, 6 H, СОMе and SMе);
3.69 (m, 2 H, СН2N); 7.49 (m, 3 H, Ph); 8.49 (m, 2 H, Ph); 9.51 (br.t, 1 Н, NH)
2.31 (s, 3 H, NMе); 2.51 (m, 4 H, 2 СН2N); 2.82 (s, 3 H, MеCO); 3.70 (m, 4 H, 2 СН2N); 7.58 (m, 3 H, Ph);
7.97 (m, 2 H, Ph); 10.02 (br.s, 1 Н, NH)
2.85 (s, 3 H, MеCO); 3.18 (m, 4 H, 2 СН2N); 3.80 (s, 3 H, OMe); 3.85 (m, 4 H, 2 СН2N); 6.88 (m, 4 H, C6H4);
7.58 (m, 3 H, Ph); 7.98 (m, 2 H, Ph); 10.25 (br.s, 1 Н, NH)
9b
9c
9d
9e
9f
2.85 (s, 3 H, MеCO); 3.21 (m, 4 H, 2 СН2N); 3.82 (m, 4 H, 2 СН2N); 6.85 (m, 2 H, C6H4); 6.94 (m, 2 H, C6H4);
7.60 (m, 3 H, Ph); 7.98 (m, 2 H, Ph); 10.32 (br.s, 1 Н, NH)
2.32 (s, 6 H, 2 Mе); 3.32 (s, 3 H, СОMе); 6.87 (s, 1 H, рꢀHC H ); 7.21 (s, 2 H, oꢀHC H ); 7.56 (t, 2 Н, mꢀHPh, J = 7.8);
6
7.65 (t, 1 Н, рꢀHPh, J = 7.8); 7.91 (m, 2 H, оꢀHPh); 10.28 (br6.s,31 Н, NH); 12.43 (br.s, 31 Н, NHC6H3)
3.04 (s, 3 H, СОMе); 7.21 (d, 1 H, рꢀHC H , J = 7.8); 7.31 (t, 1 H, mꢀHC H , J = 7.8); 7.40 (d, 1 H, oꢀHC H , J = 7.8);
6
4
6
4
7.59 (t, 2 H, mꢀHРh, J = 7.8); 7.66 (t, 1 H, pꢀHРh, J = 7.8); 7.81 (s, 1 H, оꢀHC H ); 7.99 (d, 2 H, оꢀHPh, J 6= 47.8);
6
4
10.31 (br.s, 1 Н, NH); 12.64 (br.s, 1 Н, NHC6H4)
9g
9h
9i
3.04 (s, 3 H, СОMе); 7.41—7.74 (m, 6 H, mꢀHPh, pꢀHPh, oꢀHC H , mꢀHC H , рꢀHC H ); 7.99 (d, 2 H, оꢀHPh, J = 7.8);
6 4 4 6 4
8.20 (s, 1 H, оꢀHC H ); 10.38 (br.s, 1 Н, NH); 12.75 (br.s, 1 Н, NHC6H4) 6
6
3.00 (s, 3 H, СОMе)4; 4.91 (d, 2 H, CH2, J = 5.0); 7.32 (m, 5 H, PhCH2); 7.56 (t, 2 H, mꢀHРh, J = 7.8);
7.63 (t, 1 H, рꢀHРh, J = 7.8); 7.99 (d, 2 H, оꢀHPh, J = 7.8); 10.22 (br.s, 1 Н, NH); 11.10 (br.t, 1 Н, NHCH2)
0.96 (t, 3 H, MеСН2, J = 7.2); 1.42 (m, 2 H, СН2); 1.69 (m, 2 H, СН2); 2.98 (s, 3 H, СОMе); 3.68 (m, 2 H, СН2N);
7.56 (t, 2 H, mꢀHРh, J = 7.8); 7.62 (t, 1 H, рꢀHРh, J = 7.8); 8.01 (d, 2 H, оꢀHPh, J = 7.8); 10.11 (br.s, 1 Н, NH);
10.78 (br.t, 1 Н, NHCH2)
14а
14b
2.79 (s, 3 H, MеCO); 3.40 (s, 3 H, SО2Mе); 6.62 (br.s, 2 H, NН2); 7.50 (m, 3 H, Ph); 8.35 (d, 2 H, Ph, J = 7.8)
2.38 (s, 6 H, 2 Mе); 2.84 (s, 3 H, MеCO); 3.41 (s, 3 H, SO2Me); 6.87 (s, 1 H, pꢀHC H ); 7.31 (s, 2 H, oꢀHC H );
6
3
6
3
7.51 (m, 3 H, Ph); 8.38 (d, 2 H, Ph, J = 7.8); 8.91 (br.s, 1 Н, NH)
2.88 (s, 3 H, MеCO); 3.42 (s, 3 H, SО2Mе); 7.19 (d, 1 H, pꢀHC H , J = 7.8); 7.36 (t, 1 H, mꢀHC H , J = 7.8);
14c
6
4
7.45 (d, 1 H, оꢀHC H , J = 7.8); 7.53 (m, 3 H, mꢀHPh, рꢀHРh); 7.941 (s, 1 H, оꢀHC H ); 8.48 (d, 26H, оꢀHPh, J = 7.8);
6
6
4
9.12 (br.s, 1 Н, NH) 4
14d
2.91 (s, 3 H, MеCO); 3.45 (s, 3 H, SО2Mе); 7.43—7.62 (m, 5 H, рꢀHC H , mꢀHC H , mꢀHPh, рꢀHРh);
6 4 6 4
7.66 (d, 1 H, оꢀHC H , J = 7.8); 8.31 (s, 1 H, оꢀHC H ); 8.39 (d, 2 H, оꢀHPh, J = 7.8); 9.30 (br.s, 1 Н, NH)
6
4
6
14e**
2.79 (s, 3 H, MеСО); 3.39 (s, 3 H, SО2Mе); 4.86 (d, 42 H, CH2, J = 6.0); 7.32 (m, 1 H, рꢀHPhCH ); 7.38 (m, 4 Н,
2
оꢀHPhCH , mꢀHPhCH ); 7.43 (br.t, 1 Н, NH); 7.50 (t, 2 H, mꢀHPh, J = 7.8); 7.55 (t, 1 H, рꢀHPh, J = 7.8);
2
2
8.40 (d, 2 H, оꢀHPh, J = 7.8)
14f
0.98 (t, 3 H, MеСН2, J = 7.2); 1.44 (m, 2 H, СН2); 1.69 (m, 2 H, СН2); 2.78 (s, 3 H, СОMе); 3.39 (s, 3 H, SО2Mе);
3.67 (m, 2 H, СН2N); 7.10 (br.t, 1 H, NH); 7.51 (m, 3 H, Ph); 8.40 (d, 2 H, Ph, J = 7.8)
* Here and in the 1H NMR spectra reported below, positions of the protons in disubstituted and trisubstituted benzene rings are given
with respect to the carbon atom bonded the nitrogen atom.
** The spectrum was recorded on a spectrometer with the operational frequency of 600 MHz.

4ꢀAminopyrazolo[3,4ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
339
Table 3. Yields, melting points, and elemental analysis data for
pyrazolopyrimidines 10a—i, 11a—f
was added, a precipitate formed was filtered off to obtain a white
substance (0.074 g) (two close spots on a TLC plate with the
Rf values of 0.18 and 0.24 in the system chloroform—EtOH 20 : 1).
According to the 1H NMR spectrum, this is a mixture of two
compounds 12a and 13a in molar ratio ~2 : 1. 1H NMR of comꢀ
pound 12a (CDCl3), : 2.19 (s, 3 H, Me); 2.70 (s, 3 H, SMe);
4.88 (br.s, 2 H, NH2); 5.28 (br.s, 2 H, NH2); 7.48 (m, 3 H, Ph);
8.42 (m, 2 H, Ph). 1H NMR of compound 13a (CDCl3), : 2.17
(s, 6 H, 2 Me); 2.70 (s, 6 H, 2 SMe); 5.50 (br.s, 4 H, 2 NH2); 7.48
(m, 6 H, 2 Ph); 8.42 (m, 4 H, 2 Ph).
Comꢀ Yield
pound (%)
M.p.
/C
Found
Calculated
Molecular
formula
(%)
N
С
H
10a
10b
10c
10d
10e
10f
62 240—241 65.17 5.89 24.04 С16H17N5O
65.07 5.80 23.71
81 230—231 65.85 6.31 26.96 С17H20N6
66.21 6.54 27.25
72 218—219 69.01 6.27 21.00 С23H24N6O
68.98 6.04 20.99
61 218—219 67.79 5.41 21.71 С22H21FN6
68.02 5.45 21.64
62 317—320 63.71 4.89 30.79 С12H11N5
63.99 4.92 31.09
80 272—273 72.70 5.85 20.91 С20H19N5
72.92 5.81 21.26
Reaction of 5ꢀacetylꢀ4ꢀ(3,5ꢀdimethylphenylamino)ꢀ4ꢀmethylꢀ
sulfanylꢀ2ꢀphenylpyrimidine (4e) with hydrazine hydrate. A mixꢀ
ture of pyrimidine 4e (0.082 g, 0.23 mmol) and hydrazine hyꢀ
drate (0.27 mL, 5.6 mmol) in butanol (5 mL) was refluxed for
4 h, the solvent and excess hydrazine were evaporated in vacuo,
the residue was washed with light petroleum to obtain a mixture
of compounds 12b and 13b (0.061 g) in the ratio ~8 : 1. 1H NMR
of compound 12b (CDCl3), : 2.19 (s, 3 H, Me); 2.35 (s, 6 H,
2 Me); 2.72 (s, 3H, SMe); 5.60 (br.s, 2 H, NH2); 6.75 (s, 1 H,
pꢀHC H ); 7.36 (s, 2 H, oꢀHC H ); 7.48 (m, 3 H, Ph); 8.38 (br.s,
3
6
3
1 H, 6NH); 8.49 (m, 2 H, Ph). 1H NMR of compound 13b
(CDCl3), : 2.21 (s, 6 H, 2 Me); 2.35 (s, 12 H, 4 Me); 2.72
(s, 6 H, 2 SMe); 6.75 (s, 2 H, 2 C6H3); 7.36 (s, 4 H, 2 C6H3);
7.48 (m, 6 H, 2 Ph); 8.49 (m, 4 H, 2 Ph).
10g
10h
10i
74 301—303 64.11 4.10 20.73 С18H14ClN5
64.38 4.20 20.86
80 264—265 61.54 3.77 18.59 С18H14F3N5
61.79 3.82 18.96
76 215—216 72.09 5.28 22.05 С19H17N5
72.36 5.43 22.21
4ꢀMethylsulfonylpyrimidines (14a—d). A mixture of the corꢀ
responding 4ꢀmethylsulfanylpyrimidine 3,4e—g (0.5 mmol) and
40% MCPBA (0.54 g, 1.25 mmol) in chloroform (14 mL) was
stirred for 30 min at ~20 C, chloroform was evaporated in vacuo
at ~20 C, benzene (12 mL) was added to the residue, a precipiꢀ
tate of mꢀchlorobenzoic acid was filtered off, the filtrate was
shaken with saturated aqueous K2CO3, the organic layer was
separated and, without concentration, was subjected to column
chromatography on SiO2 (eluent benzene). The solvent was
evaporated in vacuo, the residue was washed with light petroꢀ
leum (5 mL) to obtain pyrimidines 14a—d as colorless crystals.
The yields, melting points, and elemental analysis data are given
in Table 1, the 1H NMR spectra, in Table 2.
5ꢀAcetylꢀ6ꢀaminoꢀ4ꢀmethylsulfonylꢀ2ꢀphenylpyrimidine (14a).
MS, m/z (Irel (%)): 291 [M]+ (70), 276 [M – Me]+ (94), 228
[M – SOMe]+ (24), 214 [M – Ph]+ (60), 104 [PhC=NH]+ (100),
76 (78), 67 (91). IR (CHCl3), /cm–1: 3512 and 3400 (NH2),
1680 (CO), 1604, 1552, 1508.
5ꢀAcetylꢀ6ꢀ(3,5ꢀdimethylphenylamino)ꢀ4ꢀmethylsulfonylꢀ2ꢀ
phenylpyrimidine (14b). MS, m/z (Irel (%)): 395 [M]+ (100), 316
[M – SO2Me]+ (63). IR (CHCl3), /cm–1: 3370 (NH), 1676
(CO), 1616, 1572, 1548.
5ꢀAcetylꢀ6ꢀ(3ꢀchlorophenylamino)ꢀ4ꢀmethylsulfonylꢀ2ꢀphenylꢀ
pyrimidine (14c). MS, m/z (Irel (%)): 401 [M]+ (15), 322 [M –
– SO2Me]+ (12), 276 [M – ClC6H4N]+ (15), 219 [M – SO2Me –
– PhCN]+ (33), 177 [M – SO2Me – PhCN – CH2CO]+ (100).
IR (KBr), /cm–1: 3356 (NH), 1676 (CO), 1592, 1564, 1536.
5ꢀAcetylꢀ4ꢀmethylsulfonylꢀ2ꢀphenylꢀ6ꢀ(3ꢀtrifluoromethylꢀ
phenylamino)pyrimidine (14d). MS, m/z (Irel (%)): 435 [M]+ (100),
356 [M – SO2Me]+ (19), 355 [M – SO2Me – H]+ (22), 253
[M – SO2Me – PhCN]+ (13), 211 [M – SO2Me – PhCN –
– CH2CO]+ (25). IR (KBr), /cm–1: 3280 (NH), 1684 (CO),
1604, 1588, 1552.
11a
11b
11c
11d
11e
11f
57 131—132 65.64 6.01 22.38 С17H19N5O
66.00 6.19 22.64
48 159—160 67.00 7.10 25.84 С18H22N6
67.06 6.87 26.07
64 184—185 69.43 6.27 20.08 С24H26N6O
69.54 6.32 20.28
26 198—199 68.45 5.54 20.74 С23H23FN6
68.64 5.76 20.88
55 170—171 65.02 5.25 28.98 С13H13N5
65.25 5.48 29.27
65 195—196 73.12 6.23 20.34 С21H21N5
73.44 6.16 20.39
1,3ꢀDimethylꢀ4ꢀ(4ꢀmethylpiperazinꢀ1ꢀyl)ꢀ6ꢀphenylꢀ1Hꢀpyrꢀ
azolo[3,4ꢀd]pyrimidine (11b). MS, m/z (Irel (%)): 322 [M]+ (1), 252
[M – MeN(CH)CH2CH2]+ (100), 240 [M – MeN(CH2C)ꢀ
CH2CH]+ (44), 223 [M – MeN(CH2)4N]+ (59). IR (CHCl3),
/cm–1: 1564, 1548.
4ꢀ[4ꢀ(4ꢀMethoxyphenyl)piperazinꢀ1ꢀyl]ꢀ1,3ꢀdimethylꢀ6ꢀpheꢀ
nylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine (11c). IR (CHCl3), /cm–1
:
1580, 1552, 1512.
4ꢀ[4ꢀ(4ꢀFluorophenyl)piperazinꢀ1ꢀyl]ꢀ1,3ꢀdimethylꢀ6ꢀpheꢀ
nylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine (11d). MS, m/z (Irel (%)):
402 [M]+ (3), 265 [M – FC6H4NCH2CH2]+ (32), 252 [M –
–
FC6H4N(CH)CH2CH2]+ (100), 238 [M
– FC6H4Nꢀ
(CHCH2)CH2CH2]+ (35), 223 [M – FC6H4N(CH2)4N]+ (57).
IR (CHCl3), /cm–1: 1552, 1512.
Reaction of 5ꢀacetylꢀ6ꢀaminoꢀ4ꢀmethylsulfanylꢀ2ꢀphenylpyrꢀ
imidine (3) with hydrazine hydrate. A mixture of pyrimidine 3
(0.10 g, 0.4 mmol) and hydrazine hydrate (0.5 mL, 10 mmol) in
butanol (5 mL) was refluxed for 6 h, the solvent and excess
hydrazine was evaporated in vacuo, benzene (5 mL) was added
to the residue to the residue, which was dissolved by heating,
then the mixture was cooled to 20 C, light petroleum (5 mL)
5ꢀAcetylꢀ6ꢀbenzylaminoꢀ4ꢀmethylsulfonylꢀ2ꢀphenylpyrimidine
(14e) and 5ꢀacetoxyꢀ6ꢀbenzylaminoꢀ4ꢀmethylsulfonylꢀ2ꢀphenylꢀ
pyrimidine (15e). Oxidation of pyrimidine 4h and workꢀup of the
reaction mixture were carried out similarly to those in the prepaꢀ

340
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Komkov et al.
Table 4. The 1H NMR spectra of pyrazolopyrimidines 10a—i, 11a—f
Comꢀ
pound
Solvent
, J/Hz
10а
10b
10c
CDCl3
CDCl3
CDCl3
2.66 (s, 3 H, Ме); 3.92 (s, 8 H, 2 СН2N and 2 СН2O); 7.50 (m, 3 H, Ph); 8.49 (m, 2 H, Ph);
11.65 (br.s, 1 H, NH)
2.42 (s, 3 H, NМе); 2.65 (m, 4 H, 2 СН2N); 2.66 (s, 3 H, Ме); 3.98 (m, 4 H, 2 СН2N);
7.51 (m, 3 H, Ph); 8.50 (m, 2 H, Ph); 11.50 (br.s, 1 Н, NH)
2.71 (s, 3 H, Ме); 3.30 (m, 4 H, 2 СН2N); 3.82 (s, 3 H, OMe); 4.10 (m, 4 H, 2 СН2N);
6.88 (d, 2 H, C6H4, J = 7.8); 6.97 (d, 2 H, C6H4, J = 7.8); 7.51 (m, 3 H, Ph); 8.51 (m, 2 H, Ph);
11.68 (br.s, 1 Н, NH)
10d
CDCl3
2.71 (s, 3 H, Ме); 3.32 (m, 4 H, 2 СН2N); 4.03 (m, 4 H, 2 СН2N); 6.99 (m, 4 H, C6H4);
7.52 (m, 3 H, Ph); 8.52 (m, 2 H, Ph); 11.89 (br.s, 1 Н, NH)
10e
10f*
DMSOꢀd6
DMSOꢀd6
2.53 (s, 3 H, Ме); 7.18 (br.s, 2 H, NH2); 7.49 (m, 3 H, Ph); 8.37 (m, 2 H, Ph); 12.95 (br.s, 1 Н, NH)
2.34 (s, 6 H, 2 Ме); 2.69 (s, 3 H, Ме); 6.80 (s, 1 H, рꢀHC H ); 7.48 (m, 3 H, mꢀHPh, pꢀHРh);
6
3
7.52 (s, 2 H, oꢀHC H ); 8.35 (m, 2 H, оꢀHРh); 8.50 (br.s, 1 Н, NHC6H3); 13.23 (br.s, 1 Н, NH)
3
10g
10h
10i
DMSOꢀd6
DMSOꢀd6
DMSOꢀd6
2.72 (s, 3 H, Ме); 67.19 (d, 1 H, рꢀHC H , J = 7.8); 7.48 (m, 4 H, mꢀHРh, pꢀHРh, mꢀHC H );
6
6
4
7.82 (d, 1 H, oꢀHC H , J = 7.8); 8.10 (s,41 H, оꢀHC H ); 8.36 (m, 2 H, оꢀHPh); 8.80 (br.s, 1 Н,
6
4
6
4
NHC6H4); 13.31 (br.s, 1 Н, NH)
2.74 (s, 3 H, Ме); 7.45 (m, 4 H, mꢀHРh, pꢀHРh, pꢀHC H ); 7.68 (t, 1 H, mꢀHC H , J = 7.8);
6
4
4
8.08 (d, 1 H, oꢀHC H , J = 7.8); 8.34 (m, 2 H, оꢀHPh); 8.48 (s, 1 H, оꢀHC H );6
6
6
4
8.95 (br.s, 1 Н, NH);413.37 (br.s, 1 Н, NH)
2.61 (s, 3 H, Ме); 4.87 (d, 2 H, CH2, J = 5.4); 7.21 (t, 1 H, рꢀHPhCH , J = 7.2); 7.31 (t, 2 Н,
mꢀHPhCH , J = 7.2); 7.43 (m, 3 Н, mꢀHPh, рꢀHPh); 7.46 (d, 2 H, оꢀH2PhCH , J = 7.2); 7.80 (br.t, 1 H,
2
2
NHCH2); 8.33 (m, 2 Н, оꢀHPh); 13.05 (br.s, 1 Н, NH)
11а*
11b
11c
11d
CDCl3
CDCl3
CDCl3
CDCl3
2.61 (s, 3 H, Ме); 3.87 (m, 4 H, 2 СН2N); 3.88 (m, 4 H, 2 СН2O); 4.03 (s, 3 H, NМе);
7.46 (m, 3 H, Ph); 8.51 (m, 2 H, Ph)
2.41 (s, 3 H, NМе); 2.63 (s, 3 H, Ме); 2.68 (m, 4 H, 2 СН2N); 3.93 (m, 4 H, 2 СН2N);
4.03 (s, 3 H, NМе); 7.48 (m, 3 H, Ph); 8.51 (m, 2 H, Ph)
2.68 (s, 3 H, Ме); 3.29 (m, 4 H, 2 СН2N); 3.79 (s, 3 H, OMe); 4.04 (m, 7 H, 2 СН2N and NМе);
6.88 and 6.96 (both d, 2 H each, C6H4, J = 7.5); 7.49 (m, 3 H, Ph); 8.55 (m, 2 H, Ph)
2.68 (s, 3 H, Ме); 3.31 (m, 4 H, 2 СН2N); 4.02 (m, 4 H, 2 СН2N); 4.04 (s, 3 H, NМе);
6.98 (m, 4 H, C6H4); 7.49 (m, 3 H, Ph); 8.52 (m, 2 H, Ph)
11e
11f*
CDCl3
CDCl3
2.61 (s, 3 H, Ме); 4.01 (s, 3 H, NМе); 5.62 (br.s, 2 H, NH2); 7.47 (m, 3 H, Ph); 8.44 (m, 2 H, Ph)
2.41 (s, 6 H, 2 Ме); 2.71 (s, 3 H, Ме); 4.04 (s, 3 H, NМе); 6.83 (s, 1 H, рꢀHC H );
6
3
6.90 (br.s, 1 Н, NH); 7.50 (m, 5 H, mꢀHPh, pꢀHРh, oꢀHC H ); 8.55 (m, 2 H, оꢀHРh
)
6
3
* The spectra were recorded on a spectrometer with the operational frequency of 600 MHz.
ration of pyrimidines 14a—d. Isolation was performed by colꢀ
umn chromatography on SiO2 (eluent benzene, then a 4 : 1 mixꢀ
ture of benzene and chloroform, then chloroform). The first
fractions contained pyrimidine 14e (yield 44%), whereas the folꢀ
lowing fractions contained pyrimidine 15e (yield 11%). Pyrimiꢀ
dine 14e (m.p., elemental analysis data, and 1H NMR spectrum
see Tables 1 and 2), MS, m/z (Irel (%)): 381 [M]+ (74), 303 [M –
– CH2SO2]+ (35), 302 [M – SO2Me]+ (30), 225 [M – SO2Me –
– Ph]+ (24), 91 [PhCH2]+ (100). IR (KBr), /cm–1: 3334 (NH),
1681 (CO), 1588, 1570, 1496. 13C NMR (CDCl3), : 33.98
(MeCO); 40.58 (MeSO2); 45.50 (CH2); 110.11 (C(5)); 127.63
(oꢀCPhCH ); 127.68 (pꢀCPhCH ); 128.51 (mꢀCPh); 128.71 (oꢀCPh);
Calculated (%): C, 60.44; H, 4.82; N, 10.57; S, 8.07. HRMS
(MCBP): found: m/z 420.0989 [M + Na]+; 396.1022 [M – H]–;
C20H19N3O4S; calculated: [M + Na]+ = 420.0988; [M – H]–
=
= 396.1024. IR (KBr), /cm–1: 3347 (NH), 1779 (CO2), 1595,
1577, 1498. 1H NMR (CDCl3), : 2.40 (s, 3 H, Me); 3.33 (s, 3 H,
MeSO2); 4.87 (d, 2 H, CH2, J = 4.8 Hz); 5.64 (br.s, 1 H, NH);
7.32 (m, 1 H, pꢀHPhCH ); 7.37 (m, 4 H, oꢀHPhCH , mꢀHPhCH );
2
7.48 (m, 3 H, mꢀHPh, p2ꢀHPh); 8.23 (d, 2 H, oꢀHPh2, J = 7.2 Hz).
13C NMR (CDCl3), : 20.85 (MeCO2); 39.86 (MeSO2); 45.15
(CH2); 126.34 (C(5)); 127.68 (oꢀCPhCH ); 127.82 (pꢀCPhCH );
2
128.39 (mꢀCPh); 128.41 (oꢀCPh); 128.828 (mꢀCPhCH ); 131.09
(pꢀCPh); 136.25 (ipsoꢀCPh); 137.67 (ipsoꢀCPhCH ); 152.275 (C(4));
2
2
2
128.80 (mꢀCPhCH ); 131.93 (pꢀCPh); 135.84 (ipsoꢀCPh); 137.61
157.47 (C(6)); 161.01 (C(2)); 168.50 (CO2). The signals were
assigned based on the 2D 1H/13C HSQC and HMBC spectra.
15N NMR (CDCl3), :* –287 (NH), (correlations with the
protons NH and CH2), –130 (N(1)), (correlation with the proꢀ
ton NH).
2
(ipsoꢀCPhCH ); 159.94 (C(6)); 162.89 (C(4)); 163.84 (C(2));
201.54 (CO)2. The signals were assigned based on the 2D 1H/13
C
HSQC and HMBC spectra. 15N NMR (CDCl3), :* –278 (NH),
(correlations with the protons NH and CH2), –133 (N(1)), (corꢀ
relation with the proton NH). Pyrimidine 15e, m.p. 172—173 C.
Found (%): C, 60.08; H, 4.78; N, 10.18; S, 7.94. C20H19N3O4S.
5ꢀAcetylꢀ6ꢀbutylaminoꢀ4ꢀmethylsulfonylꢀ2ꢀphenylpyrimidine
(14f) and 5ꢀacetoxyꢀ6ꢀbutylaminoꢀ4ꢀmethylsulfonylꢀ2ꢀphenylꢀ
* Chemical shifts were measured based on the analysis of the 2D 1H/15N HMBC spectrum.

4ꢀAminopyrazolo[3,4ꢀd]pyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
341
pyrimidine (15f) were synthesized similarly to compounds 14e
and 15e from pyrimidine 4i. Pyrimidine 14f (24%) and pyrꢀ
imidine 15f (11%) was obtained, m.p. 148—149 C. Found (%):
C, 56.35; H, 6.01; N, 11.81; S, 8.68. C17H21N3O4S. Calcuꢀ
lated (%): C, 56.18; H, 5.82; N, 11.56; S, 8.82. MS,
m/z (Irel (%)): 363 [M]+ (6), 321 [M – CH2CO]+ (100), 304
[M – MeCO2]+ (21), 292 [M – C4H9N]+ (65), 278 [M – CH2CO –
– C3H7]+ (49), 265 [M – BuNHCN]+ (30), 241 [M – MeSO2 –
– MeCO]+ (50), 104 [PhC=NH]+ (49). IR spectrum of 14f
(KBr), /cm–1: 3345 (NH), 1684 (CO), 1590, 1575, 1480 (see
also Tables 1 and 2). IR spectrum of 15f (KBr), /cm–1: 3378
(NH), 1785 (CO2), 1599, 1582, 1511. 1H NMR (CDCl3), : 0.98
(t, 3 H, MeCH2, J = 7.2 Hz); 1.44 (m, 2 H, CH2); 1.69 (m, 2 H,
CH2); 2.42 (s, 3 H, MeCO2); 3.32 (s, 3 H, MeSO2); 3.67 (m, 2 H,
NCH2); 5.30 (br.t, 1 H, NH); 7.51 (m, 3 H, Ph); 8.37 (d, 2 H,
Ph, J = 7.5 Hz).
HMBC spectrum. 15N NMR (DMSOꢀd6), :* –287 (NH), (corꢀ
relations on the protons NH and CH2), –164 (N(5)), (correlaꢀ
tion on the proton NH), –85 (N(2)), (correlations on the proꢀ
tons of the Me group).
1ꢀMethylpyrazolo[3,4ꢀd]pyrimidines (11e,f). A mixture of the
corresponding 4ꢀmethylsulfonylpyrimidine 14a,b (0.5 mmol) and
methylhydrazine (0.27 mL, 5 mmol) in BuOH (10 mL) was reꢀ
fluxed for 2 h, butanol and excess methylhydrazine were evapoꢀ
rated in vacuo, the residue was subjected to column chromatogꢀ
raphy on SiO2 (eluent chloroform). the solvent was evaporated
in vacuo, the residue was crystallized with light petroleum (5 mL)
to obtain compounds 11e,f as colorless crystals. Analytically pure
samples were obtained by recrystallization from a 1 : 1 mixture
of benzene—hexane. The yields, melting points, and elemenꢀ
tal analysis data are given in Table 3, the 1H NMR spectra,
in Table 4.
Pyrazolo[3,4ꢀd]pyrimidines (10e—i). A mixture of the correꢀ
sponding 4ꢀmethylsulfonylpyrimidine 14a—e (0.5 mmol) and
hydrazine hydrate (0.5 mL, 10 mmol) in BuOH (10 mL) was
refluxed for 2 h, cooled to 20 C. A formed precipitate of pyraꢀ
zolopyrimidine 10g was filtered off. in other cases butanol and
excess hydrazine were evaporated in vacuo, the residue was reꢀ
crystallized from acetonitrile to obtain compounds 10e,f,l as colꢀ
orless crystals. Pyrazolopyrimidine 10h was obtained after diluꢀ
tion of acetonitrile with water. For elemental analysis, pyrazoloꢀ
pyrimidine 10e additionally was recrystallized from methanol.
The yields, melting points, and elemental analysis data are given
in Table 3, the 1H NMR spectra, in Table 4.
4ꢀAminoꢀ1,3ꢀdimethylꢀ6ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidꢀ
ine (11e). MS, m/z (Irel (%)): 239 [M]+ (100), 136 [M – PhCN]+
(37), 104 [PhC=NH]+ (37). IR (KBr), /cm–1: 3496 and 3304
(NH2), 3104, 1648, 1592, 1568, 1520. 13C NMR (CDCl3), :
14.61 (Me); 33.30 (NMe); 98.39 (C(3a)); 128.28 (mꢀCPh); 128.42
(oꢀCPh); 130.25 (pꢀCPh); 138.12 (ipsoꢀCPh); 139.98 (C(3)); 155.90
(C(7a)); 157.98 (C(4)); 162.25 (C(6)). The signals were assigned
based on the 2D 1H/13C HMBC spectrum.
1,3ꢀDimethylꢀ4ꢀ(3,5ꢀdimethylphenylamino)ꢀ6ꢀphenylꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (11f). MS, m/z (Irel (%)): 343 [M]+
(100), 328 [M – Me]+ (6). IR (KBr), /cm–1: 3448 (NH), 3020,
2916, 1620, 1596, 1584, 1564, 1508. 13C NMR (CDCl3), : 14.93
4ꢀAminoꢀ3ꢀmethylꢀ6ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrimidine
(10e). MS, m/z (Irel (%)): 225 [M]+ (100), 122 [M – PhCN]+
(26), 104 [PhC=NH]+ (60), 76 (85). IR (KBr), /cm–1: 3424
(NH), 3312 (NH), 3184, 1636, 1592, 1568, 1472.
4ꢀ(3,5ꢀDimethylphenylamino)ꢀ3ꢀmethylꢀ6ꢀphenylꢀ1Hꢀpyrꢀ
azolo[3,4ꢀd]pyrimidine (10f). MS, m/z (Irel (%)): 329 [M]+ (100),
328 [M – H]+ (92), 314 [M – Me]+ (11), 209 [M –
– Me2C6H3NH]+ (24). IR (KBr), /cm–1: 3428 (NH), 3132,
2924, 2852, 1624, 1600, 1588, 1568, 1500. 13C NMR (DMSOꢀd6),
(Me); 21.46 (2 Me); 33.32 (NMe); 99.02 (C(3a)); 118.81 (oꢀCC H );
3
125.65 (pꢀCC H ); 128.27 (mꢀCPh); 128.57 (oꢀCPh); 1360.30
6
(pꢀCPh); 138.35 (i3psoꢀCPh); 138.47 (ipsoꢀCC H ); 138.64 (mꢀCC H );
6
3
3
138.89 (C(3)); 155.05 (C(4)); 155.87 (C(7a)); 161.92 (C(6)).6The
signals were assigned based on the 2D 1H/13C HMBC spectrum.
15N NMR (CDCl3), :* –267 (NH, correlations with the proꢀ
tons NH and oꢀC6H3), –200 (N(1), correlation with the protons
of the NMe group), –153 (N(5), correlation with the proton
NH), –72 (N(2), correlations with the protons of the NMe and
Me groups).
: 14.64 (Me); 21.06 (2 Me); 98.33 (C(3a)); 120.06 (oꢀCC H );
3
124.95 (pꢀCC H ); 127.81 (mꢀCPh); 128.34 (oꢀCPh); 1360.21
4ꢀ(3,5ꢀDimethylphenylamino)ꢀ3ꢀmethylꢀ2,6ꢀdiphenylꢀ2Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (16a). A mixture of 4ꢀmethylsulfonylꢀ
pyrimidine 14b (40 mg, 0.1 mmol) and phenylhydrazine (0.1 mL,
1 mmol) in BuOH (4 mL) was refluxed for 2 h, butanol was
evaporated in vacuo, the residue (oil) was dissolved in benzene
(4 mL) and diluted with light petroleum (16 mL). A precipitate
formed was filtered off and recrystallized from benzene to obtain
a colorless compound 16a (12 mg, 29%), m.p. 228—229 C.
Found (%): C, 76.62; H, 5.58; N, 16.95. C26H23N5. Calculatꢀ
ed (%): C, 77.01; H, 5.72; N, 17.27. MS, m/z (Irel (%)): 405
[M]+ (100), 227 (7), 219 (8), 148 (18), 101 (57), 57 (78). IR
(KBr), /cm–1: 3444 (NH), 3012, 2916, 1620, 1596, 1552, 1528,
6
3
(pꢀCPh); 137.25 (mꢀCC H ); 138.19 (ipsoꢀCC H ); 138.88 (ipsoꢀCPh);
6
3
6 3
140.64 (C(3)); 154.86 (C(4)); 157.26 (C(7a)); 160.16 (C(6)). The
signals were assigned based on the 2D 1H/13C HMBC spectrum.
4ꢀ(3ꢀChlorophenylamino)ꢀ3ꢀmethylꢀ6ꢀphenylꢀ1Hꢀpyrazoꢀ
lo[3,4ꢀd]pyrimidine (10g). MS, m/z (Irel (%)): 335 [M]+ (76),
334 [M – H]+ (22), 209 [M – ClC6H4NH]+ (24), 104 [PhC=NH]+
(73), 77 [Ph]+ (100). IR (KBr), /cm–1: 3444 (NH), 3132, 3036,
2944, 2836, 1616, 1592, 1568, 1504.
3ꢀMethylꢀ6ꢀphenylꢀ4ꢀ(3ꢀtrifluoromethylphenylamino)ꢀ1Hꢀ
pyrazolo[3,4ꢀd]pyrimidine (10h). MS, m/z (Irel (%)): 369 [M]+
(100), 368 [M – H]+ (59), 209 [M – CF3C6H4NH]+ (17), 145
[CF3C6H4]+ (10), 104 [PhC=NH]+ (28). IR (KBr), /cm–1
:
1504. H NMR (CDCl3), : 2.41 (s, 6 H, 2 Me); 2.82 (s, 3 H,
1
3444 (NH), 3132, 1620, 1592, 1572, 1332(CF3).
Me); 6.85 (s, 1 H, pꢀHC H ); 6.95 (br.s, 1 H, NH); 7.42—7.55
6
3
4ꢀBenzylaminoꢀ3ꢀmethylꢀ6ꢀphenylꢀ1Hꢀpyrazolo[3,4ꢀd]pyrꢀ
imidine (10i). MS, m/z (Irel (%)): 315 [M]+ (88), 210 [M –
(m, 5 H, oꢀHC H , mꢀHPh, pꢀHPh); 7.55—7.62 (m, 5 H, oꢀHPhN,
6 3
mꢀHPhN, pꢀHPhN); 8.62 (m, 2 H, oꢀHPh). 13C NMR (CDCl3), :
13.69 (Me); 21.42 (2 Me); 101.17 (C(3a)); 119.34 (oꢀCC H );
– PhCH2N]+ (21), 106 [PhCH2NH]+ (100). IR (KBr), /cm–1
:
6
3
3452 (NH), 3131, 3032, 2910, 1595, 1576, 1502. 13C NMR
(DMSOꢀd6), : 14.65 (Me); 43.49 (CH2); 97.60 (C(3a)); 126.55
(pꢀCPhCH ); 127.22 (oꢀCPhCH ); 127.82 (oꢀCPh); 128.14 (mꢀ
125.95 (oꢀCPhN); 126.15 (pꢀCC H ); 128.22 (mꢀCPhN); 128.79
3
(oꢀCPh); 129.15 (pꢀCPhN); 1296.27 (mꢀCPh); 130.42 (pꢀCPh);
132.45 (C(3)); 138.00 (ipsoꢀCPhN); 138.20 (ipsoꢀCPh); 138.61
2
2
CPhCH ); 128.17 (mꢀCPh); 129.93 (pꢀCPh); 138.45 (ipsoꢀCPh);
140.312(ipsoꢀCPhCH and C(3)); 156.61 (C(4)); 157.00 (C(7a));
* Chemical shifts were measured based on the analysis of the 2D
1H/15N HMBC spectrum.
2
160.33 (C(6)). The signals were assigned based on the 2D 1H/13
C

342
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Komkov et al.
(ipsoꢀCC H ); 138.71 (mꢀCC H ); 156.27 (C(4)); 160.44 (C(7a));
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6
3
6
3
161.80 (C(6)). The signals were assigned based on the 2D 1H/13
C
HMBC spectrum. 15N NMR (CDCl3), :* –263 (NH, correlaꢀ
tions with the protons oꢀC6H3), –150 (N(2), correlations with
the protons of the Me group and the orthoꢀprotons of the NPh
group).
4ꢀButylaminoꢀ3ꢀmethylꢀ2,6ꢀdiphenylꢀ2Hꢀpyrazolo[3,4ꢀd]ꢀ
pyrimidine (16b). A mixture of 4ꢀmethylsulfonylpyrimidine 14f
(77 mg, 0.22 mmol) and phenylhydrazine (0.22 mL, 2.2 mmol)
in BuOH (5 mL) was refluxed for 3 h, butanol was evaporated
in vacuo, benzene (3 mL) and light petroleum (12 mL) were
added to the residue, the solution was decanted, an oil obtained
was dissolved in boiling benzene ((2 mL), cooled to 20 C, a preꢀ
cipitate formed by scraping was filtered off and subjected to colꢀ
umn chromatography on SiO2 (eluent chloroform). The solvent
was evaporated in vacuo, the residue was crystallized with light
petroleum (2 mL) to obtain a colorless compounds 16b (23 mg,
29%), m.p. 150—151 C. Found (%): C, 73.51; H, 6.23; N, 19.53.
C22H23N5. Calculated (%): C, 73.92; H, 6.49; N, 19.59. HRMS:
found: m/z 358.2026 [M + H]+; 380.1843 [M + Na]+; C22H23N5;
calculated: [M + H]+ = 358.2026; [M + Na]+ = 380.1846. IR
(KBr), /cm–1: 3456 (NH), 3060, 2956, 2931, 2872, 2859, 1617,
1
1596, 1560, 1504. H NMR (CDCl3), : 1.00 (t, 3 H, MeCH2,
J = 7.2 Hz); 1.48 (m, 2 H, CH2); 1.70 (m, 2 H, CH2); 2.68 (s, 3 H,
Me); 3.74 (m, 2 H, CH2N); 5.33 (br.s, 1 H, NH); 7.42—7.52
(m, 8 H, oꢀHPhN, mꢀHPhN, pꢀHPhN, mꢀHPh, pꢀHPh); 8.62 (d, 2 H,
oꢀHPh, J = 6.6 Hz). 13C NMR (CDCl3), : 13.50 (MeCH2);
13.86 (Me); 20.24 (CH2); 31.55 (CH2); 40.75 (NCH2); 100.99
(C(3a)); 125.81 (oꢀCPhN); 128.00 (mꢀCPhN); 128.59 (oꢀCPh);
128.72 (pꢀCPhN); 129.08 (mꢀCPh); 129.96 (pꢀCPh); 132.08 (C(3));
138.78 (ipsoꢀCPhN); 138.91 (ipsoꢀCPh); 158.67 (C(4)); 160.63
(C(7a)); 162.25 (C(6)). The signals were assigned based on the
2D 1H/13C HMBC spectrum. 15N NMR (CDCl3), :* –280 (NH,
correlations with the protons NH, NCH2. and NCH2CH2),
–154 (N(2), correlations with the protons of the Me and
orthoꢀprotons of the NPh group).
This work was financially supported by the Russian
Academy of Sciences (Program for Basic Research of the
Presidium of RAS "Development of Methods for Prepaꢀ
ration of Chemical Compounds and Creation of New
Materials").
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* Chemical shifts were measured based on the analysis of the 2D
1H/15N HMBC spectrum.
Received April 26, 2011;
in revised form November 2, 2011