Improved synthesis and efficient chemoselective reduction of fused tetrazoles under phase-transfer conditions

Article abstract of DOI:10.1055/s-2006-950206

Liquid-liquid phase-transfer conditions were employed in an improved synthesis of 7,9-substituted 7H-pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines and 5,7-substituted 4-amino-7H-pyrrolo[2,3-d]pyrimidines. The latter were obtained either by reductive ring clea

Full text of DOI:10.1055/s-2006-950206

PAPER
3275
Improved Synthesis and Efficient Chemoselective Reduction of Fused
Tetrazoles under Phase-Transfer Conditions
Chemoselective
Reductio
r
nof
F
use
m
dTetrazoles unde
r
a
Phase-Tran
l
sfer Conditio
D
ns . Desai,*a Rina D. Shahb
a
Loyola Center for R & D, St. Xavier’s College, Navrangpura, Ahmedabad 380009, India
E-mail: nirmaldesai_3@yahoo.com
b
Organic Synthesis Laboratory, M.G. Science Institute, Navrangpura, Ahmedabad 380009, India
Received 24 April 2006; revised 7 June 2006
Dedicated to the memory of Dr. Chaitanya G. Dave
ploited both reactions to synthesize pyrrolotetrazolopyri-
midines 2.6 In one of the methods, 5,7-substituted 4-
chloro-7H-pyrrolo[2,3-d]pyrimidines 1 were reacted with
sodium azide in the presence of ammonium chloride; the
Abstract : Liquid–liquid phase-transfer conditions were employed
in an improved synthesis of 7,9-substituted 7H-pyrrolo[3,2-e]tetra-
zolo[1,5-c]pyrimidines and 5,7-substituted 4-amino-7H-pyrro-
lo[2,3-d]pyrimidines. The latter were obtained either by reductive
ring cleavage of the former, or by one-pot synthesis from 5,7-sub- in situ generation of ammonium azide facilitated the reac-
stituted 4-chloro-7H-pyrrolo[2,3-d]pyrimidines.
tion in dimethyl sulfoxide at 90 °C. Recovery of dimethyl
sulfoxide from the reaction mixture is the main problem
associated with such reactions and the use of other sol-
vents was unsuccessful in generating the products in
quantitative yield. With a view to this problem, the syn-
thesis was improved by using liquid–liquid phase-transfer
conditions with toluene and water as solvents and Aliquat
336 (methyltrioctylammonium chloride) as the catalyst
(Scheme 1). This improved synthetic protocol enhanced
the reaction rates and the products were obtained in good
yields.
Key words: pyrrolotetrazolopyrimidines, reductive ring cleavage,
phase-transfer catalyst, Aliquat 336, 18-crown-6
The investigation of fused tetrazolopyrimidines as a po-
tent antagonist has shown that they have a wide range of
biological activities such as anticancer,1a,b anticonvul-
sant,1c anti-ulcer,1d anti-inflammatory,1e antitumor,1f anti-
hypertensive,1g
antimalarial,1h
antifolate,1i
and
antibacterial.1j Moreover, fused tetrazolopyrimidines are
capable of undergoing reductive ring cleavage to form
fused aminopyrimidines,2 which are known for their valu-
able pharmacological properties and as intermediates in
the construction of a variety of triheterocycles.3 Phase-
transfer catalysis (PTC) has been established as a wide-
spread synthetic technique.4 Reactions using phase-trans-
fer catalysis can be readily scaled up and have been used
particularly for clean and efficient processes involving
high yields, operational simplicity, mild conditions, low
cost, safety, and environmental profit. A literature survey
reveals that phase-transfer conditions have been least ex-
ploited for the synthesis and reduction of fused tetra-
zoles.5 These observations and pharmacological interest
have led us to improve the synthesis of 7,9-substituted
7H-pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 2 and their
transformation to 5,7-substituted 4-amino-7H-pyrro-
lo[2,3-d]pyrimidines 3 via reductive ring cleavage under
phase-transfer conditions. An efficient one-pot synthesis
of 3 was also achieved for the first time to form 5,7-sub-
stituted 4-chloro-7H-pyrrolo[2,3-d]pyrimidines 1 via in
situ generation of pyrrolotetrazolopyrimidines 2.
N
N
N
Cl
R1
R1
NaN3, Aliquat 336, toluene, H2O
reflux, 1–1.5 h
N
N
N
N
N
N
R2
R2
1a–i
2a–i
Scheme 1
Table 1 Synthesis of 7,9-Substituted 7H-Pyrrolo[3,2-e]tetrazo-
lo[1,5-c]pyrimidines 2a–i
2
R1
R2
Yield
Mp (°C)
Lit.
(%) Found
2a Ph
2b Ph
4-FC6H4
72
68
65
58
70
69
60
69
75
218–220
217–2191j
212–2141j
245–2471j
219–2211j
226–2281j
220–2221j
226–2286b
201–2026b
234–2366b
3-Cl-4-FC6H3
212–214
245–247
219–221
228–229
222–224
226–228
202–203
234–236
2c
4-MeOC6H4 4-FC6H4
2d 4-MeOC6H4 3-Cl-4-FC6H3
2e
2f
4-ClC6H4
4-ClC6H4
4-FC6H4
The chloro substituent present at C4 in the pyrrolo[2,3-
d]pyrimidine ring system was found to be highly reactive
towards nucleophilic substitution reactions with sodium
azide and hydrazine hydrate. Our earlier publication ex-
3-Cl-4-FC6H3
4-ClC6H4
2g 4-FC6H4
2h 4-FC6H4
4-FC6H4
2i
4-FC6H4
3-Cl-4-FC6H3
SYNTHESIS 2006, No. 19, pp 3275–3279
x
x.
x
x
.
2
0
0
6
Advanced online publication: 21.08.2006
DOI: 10.1055/s-2006-950206; Art ID: Z08606SS
© Georg Thieme Verlag Stuttgart · New York

3276
N. D. Desai, R. D. Shah
PAPER
NH2
N
N
N
N
N
Azides and tetrazoles can be viewed as latent amino func-
tionalities. While azides undergo chemoselective reduc-
tion using a novel system,7 lithium aluminum hydride,8
catalytic hydrogenation,8a–d,9 or various other reagents10 to
yield amines, tetrazoles are highly resistant to reduction.11
Dave et al.6 successfully reduced pyrrolotetrazolopyrim-
idines 2 with zinc dust and acetic acid. With respect to the
literature methods, the phase-transfer catalysis technique
has the novelty of using sodium borohydride as an effi-
cient reducing agent for tetrazoles. It affords pure prod-
ucts in high yields and offers the advantages of permitting
a one-pot conversion of 4-chloropyrrolo[2,3-d]pyrim-
idines 1a–i into 4-aminopyrrolo[2,3-d]pyrimidines 3a–i
with very simple operating conditions. Thus, in a modi-
fied procedure, two synthetic strategies based on phase-
transfer catalysis were adopted for the reductive ring
cleavage of pyrrolotetrazolopyrimidines 2 keeping sodi-
um borohydride as the reducing agent. Under liquid–liq-
uid phase-transfer conditions (Method I), Aliquat 336 was
used as the catalyst and toluene and water were preferred
as solvents whereas under solid–liquid phase-transfer
conditions (Method II), 18-crown-6 was used as the cata-
lyst along with powdered potassium hydroxide and aceto-
nitrile as the solvent. The obtained compounds 3a–i are
identical with those synthesized by condensation of 2-
Method I: NaBH4, Aliquat 336,
toluene, H2O, reflux
R1
R1
N
or
N
R2
N
N
R2
Method II: NaBH4, 18-Crown-6,
KOH, 80 °C
3a–i
2a–i
HCONH2,
DMF,
reflux
R1
CN
N
R2
NH2
4a–i
Scheme 2
Method III (one-pot-reaction):
1. NaN3, Aliquat 336, toluene,
H2O, reflux
Cl
N
N
N
N
R1
R1
N
N
2. NaBH4
N
R2
N
R2
N
1a–i
2a–i
amino-3-cyanopyrroles
(Scheme 2).
4a–i
and
formamide12
NH2
One-pot synthesis of 5,7-substituted 4-amino-7H-pyrro-
lo[2,3-d]pyrimidines 3a–i was achieved efficiently using
liquid–liquid phase-transfer catalysis conditions using tol-
uene and water as solvents and Aliquat 336 as the catalyst
(Method III); however, a higher mol% of catalyst was re-
quired. Firstly, 1 was reacted with sodium azide to form 2;
on completion of the reaction, an equivalent quantity of
powdered sodium borohydride was added portionwise to
the same reaction mixture to give 3 (Scheme 3).
R1
N
N
R2
N
3a–i
Scheme 3
Table 2 Synthesis of 5,7-Substituted 4-Amino-7H-pyrrolo[2,3-d]pyrimidines 3a–i
3
R1
R2
Yielda (%)
Method I
Mp (°C)
Found
Method II
Method III
Lit.
3a
3b
3c
3d
3e
3f
Ph
4-FC6H4
54
66
58
73
80
69
58
61
67
56
67
58
76
82
69
58
65
70
50
62
54
71
75
65
52
54
63
183–185
238–240
153–154
220–222
276–278
308–310
275–277
163–165
241–243
183–18512b
238–24012b
154–15612b
222–22312b
276–27812b
309–31012b
276–2786b
165–1666b
243–2456b
Ph
3-Cl-4-FC6H3
4-FC6H4
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
4-ClC6H4
4-FC6H4
4-FC6H4
4-FC6H4
3-Cl-4-FC6H3
4-FC6H4
3-Cl-4-FC6H3
4-ClC6H4
3g
3h
3i
4-FC6H4
3-Cl-4-FC6H3
a Overall yields for Method I and Method II from compound 2 and for Method III from compound 1.
Synthesis 2006, No. 19, 3275–3279 © Thieme Stuttgart · New York

PAPER
Chemoselective Reduction of Fused Tetrazoles under Phase-Transfer Conditions
3277
Anal. Calcd for C19H13FN6O (360.3): C, 63.33; H, 3.64; N, 23.32.
Found: C, 63.09; H, 3.45; N, 23.44.
In summary, we have described a convenient and practical
synthesis of pyrrolotetrazolopyrimidines and their reduc-
tive ring cleavage using various phase-transfer conditions.
We have also described, for the first time, a one-pot syn-
thesis of 4-amino-7H-pyrrolo[2,3-d]pyrimidines from 4-
chloro-7H-pyrrolo[2,3-d]pyrimidines using liquid–liquid
phase-transfer catalysis without the need to work up every
step. The operational simplicity of this synthetic route will
be helpful to elaborate the chemistry and bioactivity of
fused tetrazoles and aminopyrimidines.
7-(3-Chloro-4-fluorophenyl)-9-(4-methoxyphenyl)-7H-pyrro-
lo[3,2-e]tetrazolo[1,5-c]pyrimidine (2d)1j
IR (KBr): 1608, 1504 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 3.89 (s, 3 H, OCH3), 7.3–8.2 (m, 8 H,
ArH), 8.44 (s, 1 H, H5).
MS: m/z = 394 (M+).
Anal. Calcd for C19H12ClFN6O (394.8): C, 57.80; H, 3.06; N, 21.29.
Found: C, 57.65; H, 3.25; N, 21.40.
Melting points were determined by electrothermal method in open
capillary tube and are uncorrected. The IR spectra were recorded
KBr pellets on a Buck-500 spectrophotometer. The 1H NMR spec-
tra were recorded on a Bruker 300 MHz spectrometer in CDCl3 or
DMSO-d6, using TMS as internal standard. MS spectra were re-
corded on a JEOL SX-102 mass spectrometer under electron-im-
pact (EI) ionization. Elemental analyses were performed on a Carlo
Erba 1108 microanalyzer or Elementar Vario EL III microanalyzer.
The purity of the compounds was routinely checked by TLC using
silica gel G and spots were exposed to iodine vapor.
9-(4-Chlorophenyl)-7-(4-fluorophenyl)-7H-pyrrolo[3,2-e]tetra-
zolo[1,5-c]pyrimidine (2e)1j
IR (KBr): 1612, 1496 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 7.2–8.2 (m, 9 H, ArH), 8.41 (s, 1 H, H5).
MS: m/z = 364 (M+).
Anal. Calcd for C18H10ClFN6 (364.8): C, 59.27; H, 2.76; N, 23.04.
Found: C, 59.06; H, 2.59; N, 23.36.
7-(3-Chloro-4-fluorophenyl)-9-(4-chlorophenyl)-7H-pyrro-
lo[3,2-e]tetrazolo[1,5-c]pyrimidine (2f)1j
Compounds 1a–i were obtained according to procedures published
in the literature.6b,12b All the other starting materials were obtained
from commercial suppliers and were used without further purifica-
tion.
IR (KBr): 1604, 1508 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 7.2–8.23 (m, 8 H, ArH), 8.40 (s, 1 H, H5).
MS: m/z = 399 (M+).
7,9-Substituted 7H-Pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines
2a–i; General Procedure
Anal. Calcd for C18H9Cl2FN6 (399.2): C, 54.16; H, 2.27; N, 21.05.
Found: C, 54.01; H, 2.11; N, 20.88.
To a well-stirred soln of 5,7-substituted 4-chloro-7H-pyrrolo[2,3-
d]pyrimidine 1 (5 mmol) and Aliquat 336 (0.202 g, 0.5 mmol) in
toluene (25 mL) was added NaN3 (0.390 g, 6 mmol) in H2O (5 mL).
The mixture was stirred under reflux for 1–1.5 h. The progress of
the reaction was monitored by TLC. On completion, the two phases
were separated. The aqueous phase was extracted with toluene (15
mL) and the combined organic layers were washed with H2O
(10 × 2 mL) and dried (anhyd Na2SO4). The solvent was recovered
in vacuo and the oily residue obtained after distillation was treated
with chilled MeOH. The solid thus obtained was filtered off, dried,
and crystallized (DMF–EtOH, 6:4) (Table 1).
7-(4-Chlorophenyl)-9-(4-fluorophenyl)-7H-pyrrolo[3,2-e]tetra-
zolo[1,5-c]pyrimidine (2g)6b
IR (KBr): 1608, 1496 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 7.24–8.12 (m, 9 H, ArH), 8.44 (s, 1 H, H5).
MS: m/z = 364 (M+).
Anal. Calcd for C18H10ClFN6 (364.8): C, 59.27; H, 2.76; N, 23.04.
Found: C, 59.47; H, 2.81; N, 22.97.
7,9-Bis(4-fluorophenyl)-7H-pyrrolo[3,2-e]tetrazolo[1,5-c]pyri-
midine (2h)6b
IR (KBr): 1600, 1504 cm–1 (C=C, C=N ring).
7-(4-Fluorophenyl)-9-phenyl-7H-pyrrolo[3,2-e]tetrazolo[1,5-
c]pyrimidine (2a)1j
1H NMR (CDCl3): d = 7.10–8.14 (m, 9 H, ArH), 8.42 (s, 1 H, H5).
MS: m/z = 348 (M+).
IR (KBr): 1604, 1516 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 7.2–8.0 (m, 10 H, ArH), 8.41 (s, 1 H, H5).
MS: m/z = 330 (M+).
Anal. Calcd for C18H10F2N6 (348.3): C, 62.07; H, 2.89; N, 24.13.
Found: C, 62.20; H, 2.71; N, 23.98.
Anal. Calcd for C18H11FN6 (330.3): C, 65.45; H, 3.36; N, 25.44.
Found: C, 65.66; H, 3.27; N, 25.19.
7-(3-Chloro-4-fluorophenyl)-9-(4-fluorophenyl)-7H-pyrro-
lo[3,2-e]tetrazolo[1,5-c]pyrimidine (2i)6b
IR (KBr): 1608, 1504 cm–1 (C=C, C=N ring).
7-(3-Chloro-4-fluorophenyl)-9-phenyl-7H-pyrrolo[3,2-e]tetra-
zolo[1,5-c]pyrimidine (2b)1j
1H NMR (CDCl3): d = 7.16–8.24 (m, 8 H, ArH), 8.42 (s, 1 H, H5).
MS: m/z = 382 (M+).
IR (KBr): 1604, 1492 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 7.2–8.0 (m, 9 H, ArH), 8.43 (s, 1 H, H5).
MS: m/z = 364 (M+).
Anal. Calcd for C18H9ClF2N6 (382.8): C, 56.48; H, 2.37; N, 21.96.
Found: C, 56.54; H, 2.50; N, 22.08.
Anal. Calcd for C18H10ClFN6 (364.8): C, 59.27; H, 2.76; N, 23.04.
Found: C, 59.54; H, 2.50; N, 22.86.
5,7-Substituted 4-Amino-7H-pyrrolo[2,3-d]pyrimidines 3a–i :
General Procedures
7-(4-Fluorophenyl)-9-(4-methoxyphenyl)-7H-pyrrolo[3,2-e]tet-
razolo[1,5-c]pyrimidine (2c)1j
Method I: Liquid–Liquid Phase-Transfer Catalysis Conditions
A mixture of 7,9-substituted 7H-pyrrolo[3,2-e]tetrazolo[1,5-c]pyri-
midine 2 (2 mmol) and Aliquat 336 (0.202 g, 0.5 mmol), toluene (15
mL), and H2O (5 mL) was stirred on in a flat-bottom flask at 60 °C.
Powdered NaBH4 (0.302 g, 8 mmol) was added to this mixture por-
tionwise cautiously over a period of 30 min. The mixture was then
IR (KBr): 1600, 1504 cm–1 (C=C, C=N ring).
1H NMR (DMSO-d6): d = 3.91 (s, 3 H, OCH3), 7.3–8.1 (m, 9 H,
ArH), 8.41 (s, 1 H, H5).
MS: m/z = 360 (M+).
Synthesis 2006, No. 19, 3275–3279 © Thieme Stuttgart · New York

3278
N. D. Desai, R. D. Shah
PAPER
refluxed for 1 h. On completion (TLC) the aqueous phase was sep-
arated. The aqueous phase was extracted with toluene (15 mL) and
the combined organic layers were washed with H2O (10 × 2 mL)
and dried (anhyd Na2SO4). The solvent was recovered in vacuo, the
residue was treated with n-hexane and the solid thus formed was fil-
tered off, washed with cold MeOH, dried, and crystallized (EtOH–
CHCl3, 8:2) (Table 2).
1H NMR (CDCl3): d = 5.32 (s, 2 H, NH2), 7.10–8.38 (m, 10 H,
ArH).
Anal. Calcd for C18H12ClFN4 (338.8): C, 63.82; H, 3.57; N, 16.54.
Found: C, 64.03; H, 3.66; N, 16.75.
4-Amino-7-(3-chloro-4-fluorophenyl)-5-(chlorophenyl)-7H-
pyrrolo[2,3-d]pyrimidine (3f)12b
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
Method II: Solid–Liquid Phase-Transfer Catalysis Conditions
A mixture of 7,9-substituted 7H-pyrrolo[3,2-e]tetrazolo[1,5-c]pyri-
midine 2 (2 mmol), MeCN (25 mL), 18-crown-6 (0.132 g, 0.5
mmol), powdered KOH (0.841 g, 15 mmol) and powdered NaBH4
(0.302 g, 8 mmol) was heated at 80 °C for 2–2.5 h, the supernatant
reddish liquid was decanted from the solid residue and filter off. The
solvent was recovered in vacuo and the resulting oily residue was
treated with chilled MeOH. The solid thus obtained was filtered off,
washed with MeOH, dried, and crystallized (Table 2).
1H NMR (CDCl3): d = 5.30 (s, 2 H, NH2), 7.10–8.38 (m, 9 H, ArH).
Anal. Calcd for C18H11Cl2FN4 (373.2): C, 57.93; H, 2.97; N, 15.01.
Found: C, 57.99; H, 2.78; N, 15.12.
4-Amino-7-(4-chlorophenyl)-5-(4-fluorophenyl)-7H-pyrro-
lo[2,3-d]pyrimidine (3g)6b
IR (KBr): 3465, 3280 (NH), 1580, 1510 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 5.24 (s, 2 H, NH2), 7.12–8.36 (m, 10 H,
ArH).
Method III: One-Pot Reaction
Anal. Calcd for C18H12ClFN4 (338.8): C, 63.82; H, 3.57; N, 16.54.
Found: C, 63.90; H, 3.43; N, 16.42.
To the well-stirred soln of 5,7-substituted 4-chloro-7H-pyrrolo[2,3-
d]pyrimidine 1a–i (5 mmol) and Aliquat 336 (0.323 g, 0.8 mmol) in
toluene (25 mL) was added NaN3 (0.390 g, 6 mmol) in H2O (5 mL).
The mixture was stirred under reflux for 1–1.5 h. The progress of
the reaction was monitored with TLC, after the formation of pyrro-
lotetrazolopyrimidine 2a–i powdered NaBH4 (0.302 g, 8 mmol)
was added to the mixture in order to get the corresponding 4-ami-
nopyrrolo[2,3-d]pyrimidine 3a–i. The workup was effected accord-
ing to Method I (Table 2).
4-Amino-5,7-bis(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine
(3h)6b
IR (KBr): 3480, 3300 (NH), 1580, 1485 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 5.28 (s, 2 H, NH2), 7.20–8.38 (m, 10 H,
ArH).
Anal. Calcd for C18H12F2N4 (322.3): C, 67.08; H, 3.75; N, 17.38.
Found: C, 66.89; H, 3.50; N, 17.40.
4-Amino-7-(4-fluorophenyl)-5-phenyl-7H-pyrrolo[2,3-d]pyrim-
idine (3a)12b
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
4-Amino-7-(3-chloro-4-fluorophenyl)-5-(4-fluorophenyl)-7H-
pyrrolo[2,3-d]pyrimidine (3i)6b
1H NMR (CDCl3): d = 5.30 (s, 2 H, NH2), 7.10–8.38 (m, 11 H,
ArH).
IR (KBr): 3460, 3280 (NH), 1580, 1500 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 5.30 (s, 2 H, NH2), 7.18–8.34 (m, 9 H, ArH).
Anal. Calcd for C18H13FN4 (304.3): C, 71.04; H, 4.31; N, 18.41.
Found: C, 70.99; H, 4.11; N, 18.42.
Anal. Calcd for C18H11ClF2N4 (356.8): C, 60.60; H, 3.11; N, 15.70.
Found: C, 60.54; H, 3.24; N, 15.69.
4-Amino-7-(3-chloro-4-fluorophenyl)-5-phenyl-7H-pyrro-
lo[2,3-d]pyrimidine (3b)12b
Acknowledgment
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 5.32 (s, 2 H, NH2), 7.10–8.38 (m, 10 H,
We wish to thank the Regional Sophisticated Instrumentation Cen-
ter, Central Drug Research Institute, Lucknow and Chandigarh, In-
dia, for the 1H NMR and mass spectral analyses and the Director of
the Loyola Center for R & D, St. Xavier’s College, Ahmedabad, for
the facility to carry out this work.
ArH).
Anal. Calcd for C18H12ClFN4 (338.8): C, 63.82; H, 3.57; N, 16.54.
Found: C, 63.99; H, 3.78; N, 16.42.
4-Amino-7-(4-fluorophenyl)-5-(4-methoxyphenyl)-7H-pyrro-
lo[2,3-d]pyrimidine (3c)12b
References
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
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(f) Hand, E. S.; Backer, D. C. Can. J. Chem. 1984, 62, 2570.
(g) Chain, L. K.; Wei, H. S.; Khun, H. M. Tai-wan yao
Hsuch Tsa chih 1986, 38, 2428; Chem. Abstr., 1988, 108,
94490. (h) Franco, G.; Maria, L.; Guiueseppe, P. J.
1H NMR (CDCl3): d = 3.90 (s, 3 H, OCH3), 5.32 (s, 2 H, NH2),
7.10–8.38 (m, 10 H, ArH).
Anal. Calcd for C19H15FN4O (334.4): C, 68.25; H, 4.52; N, 16.76.
Found: C, 68.10; H, 4.40; N, 16.52.
4-Amino-7-(3-chloro-4-fluorophenyl)-5-(methoxyphenyl)-7H-
pyrrolo[2,3-d]pyrimidine (3d)12b
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
1H NMR (CDCl3): d = 3.89 (s, 3 H, OCH3), 5.33 (s, 2 H, NH2),
7.10–8.38 (m, 9 H, ArH).
Anal. Calcd for C19H14ClFN4O (368.8): C, 61.88; H, 3.83; N, 15.19.
Found: C, 61.99; H, 3.78; N, 15.32.
Heterocycl. Chem. 1989, 26, 613. (i) Shishoo, C. J.; Jain, S.
K. J. Heterocycl. Chem. 1992, 29, 883. (j) Dave, C. G.;
Shah, R. D. Molecules 2002, 7, 554.
4-Amino-5-(chlorophenyl)-7-(4-fluorophenyl)-7H-pyrrolo[2,3-
d]pyrimidine (3e)12b
(2) Brady, E. L.; Herbst, R. M. J. Org. Chem. 1959, 24, 922.
IR (KBr): 3470, 3290 (NH), 1585, 1500 cm–1 (C=C, C=N ring).
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Chemoselective Reduction of Fused Tetrazoles under Phase-Transfer Conditions
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Synthesis 2006, No. 19, 3275–3279 © Thieme Stuttgart · New York