A facile route to the 6-hetaryl substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives

Article abstract of DOI:10.1135/cccc20020365

Hitherto unknown 6-hetaryl-4,5,7,8-tetrahydropyrrolo[1,2-a]thieno[3,2-e]pyrimidine-4,7-diones (7a-7g) were prepared by reaction of ethyl 2-aminothiophene-3-carboxylates 5 with 4-chloro-2-hetaryl-3-oxobutanonitriles 4 in DMF at 100°C. When the same reagents were treated in the presence of triethylamine, a dependence of the reaction pathway on the nature of the hetaryl substituent in chloronitrile component was observed. This was explained in terms of steric factors.

Full text of DOI:10.1135/cccc20020365

Pyrrolo[1,2-a]thieno[3,2-e]pyrimidine Derivatives
365
A FACILE ROUTE TO THE 6-HETARYL SUBSTITUTED
PYRROLO[1,2-a ]THIENO[3,2-e]PYRIMIDINE DERIVATIVES
1,
Yulian M. VOLOVENKO, Elizaveta V. RESNYANSKA *
and Anton V. TVERDOKHLEBOV
Kiev National Taras Shevchenko University, 01033, Volodimirska str., 62, Kiev, Ukraine;
1
e-mail: atver@mail.univ.kiev.ua
Received October 23, 2001
Accepted February 8, 2002
Hith erto un kn own 6-h etaryl-4,5,7,8-tetrah ydropyrrolo[1,2-a]th ien o[3,2-e]pyrim idin e-4,7-
dion es (7a–7g) were prepared by reaction of eth yl 2-am in oth ioph en e-3-carboxylates 5 with
4-ch loro-2-h etaryl-3-oxobutan on itriles 4 in DMF at 100 °C. Wh en th e sam e reagen ts were
treated in th e presen ce of trieth ylam in e, a depen den ce of th e reaction path way on th e n a-
ture of th e h etaryl substituen t in ch loron itrile com pon en t was observed. Th is was explain ed
in term s of steric factors.
Keyw ord s: Nitrogen h eterocycles; Pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin es; Th ioph en es;
2-Am in oth ioph en e-3-carboxylates; 4-Ch loro-2-h etaryl-3-oxobutan on itriles; Heterocyclization .
As a con tin uation of our research directed to th e syn th esis of h etaryl-
substituted tricyclic h eterocycles1,2, th e preparation of th e 3-h etaryl-
pyrrolo[1,2-a]quin azolin es 1 h as been worked out3. In order to exten d our
in vestigation s in th is field, it would be in terestin g to obtain correspon din g
th ien o an alogues 2. Sin ce certain pyrroloquin azolin es like 1 were foun d to
possess several types of biological activity4, com poun ds 2 seem to be th e at-
tractive objects for screen in g. Moreover, som e th ien opyrim idin es th e m oi-
ety of wh ich is in cluded in th e rin g system of 2 were reported to exh ibit
prom isin g biological properties5.
O
N
O
N
R
NH
NH
R
S
Het
Het
O
O
1
2
Collect. Czech. Chem. Commun. (Vol. 67) (2002)
doi:10.1135/cccc20020365

366
Volovenko, Resnyanska, Tverdokhlebov:
Som e syn th eses of pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin e derivatives are
reported in th e literature6–9. All of th em utilize 2-am in oth ioph en e-
3-carboxylates or carbon itriles as startin g buildin g blocks, probably because
th ey are readily available via Gewald’s procedure10. Som e of th ese m eth ods
are step-by-step syn th etic sequen ces in cludin g in itial con struction of th e
suitably fun ction alized pyrrole rin g based on th e am in o group of startin g
am in oth ioph en e followed by pyrim idin e rin g closure6. However, th e over-
all yields of th e desired tricycles usin g th ese reaction sequen ces are low an d
th is fact m akes th em un satisfactory for preparative purposes. Corre-
spon din g tan dem syn th etic procedures seem to be m ore con ven ien t. Th ree
approach es based on th e tan dem strategy h ave been publish ed. Th e first
on e is based on reaction of 2-am in oth ioph en e-3-carboxam ides with 4-oxo-
carboxylic acids7. Th is is a good m eth od; h owever, th e n um ber of available
4-oxo acids is quite lim ited. Th e secon d way in cludes con version of
2-am in oth ioph en es in to N-ch loroacetyl derivatives, wh ich un dergo tan dem
double h eterocyclization un der treatm en t with active m eth ylen e n itriles in
alkalin e con dition s8. Fin ally, th e th ird approach allows to obtain pyrrolo-
[1,2-a]th ien o[3,2-e]pyrim idin es directly from 2-am in oth ioph en e derivatives
by treatm en t with variously substituted 4-h alobutan on itriles9. Neverth eless,
n on e of th e m en tion ed syn th etic m eth ods was applied for preparation of
h ith erto un kn own h etaryl-substituted derivatives of th e target m oiety. Th e
presen t paper reports our recen t results in th is field. It sh ould be also n oted
th at h etaryl-substituted derivatives of an isom eric system , n am ely pyrrolo-
[1,2-a]th ien o[2,3-e]pyrim idin e, h ave been prepared11
.
Reaction of Gewald’s th ioph en es with 4-h alobutan on itrile derivatives
(3rd approach ) was ch osen for th e syn th esis of th e title com poun ds because
preparation of th e required h etaryl-substituted 4-ch lorobutan on itriles
4a–4d via direct ch loroacetylation of h etarylaceton itriles 3 (Sch em e 1) was
well elaborated in our laboratory12. However, ch loron itriles 4 differ from
th e oth er 4-h alobutan on itriles used in such syn th eses previously9 by th e
presen ce of th e h eterocyclic n itrogen possessin g n ucleoph ilic properties.
Th erefore, th e in tram olecular alkylation leadin g to com poun ds like 6 can
take place as an altern ative to th e n orm al reaction path way with
am in oth ioph en es. Neverth eless, in spite of th e well-kn own low basicity of
th e am in o group of th e Gewald’s th ioph en es an d difficulty of its
alkylation 13, ch loron itriles 4a–4d were foun d to react with com poun ds 5 in
DMF at 100 °C to yield 6-h etaryl-4,5,7,8-terah ydropyrrolo[1,2-a]th ien o-
[3,2-e]pyrim idin e-4,7-dion es 7a–7g. Th e reaction probably occurs as a
th ree-step tan dem process. Th e in itial step is an alkylation of am in o group
of com poun d 5 by ch loron itrile 4. Subsequen t in tram olecular addition of
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

Pyrrolo[1,2-a]thieno[3,2-e]pyrimidine Derivatives
367
th e NH group to th e n itrile triple bon d leads to th e in term ediate am in o-
pyrrole derivative, wh ich im m ediately un dergoes in tram olecular acylation
of th e n ewly form ed am in o group by th e ester group to yield com poun d 7.
Un der n on -basic con dition s, th e m en tion ed in tram olecular alkylation was
n ot observed. Non eth eless, wh en th e reaction of ch loron itriles 4 with
am in oth ioph en es 5 was carried out in th e presen ce of trieth ylam in e, th e
beh avior of com poun ds 4a an d 4b differed from th at of 4c an d 4d . Wh en
ben zim idazolyl an d ben zoth iazolyl derivatives 4a, 4b were used as startin g
R
R
R
H
N
(i)
O
O
N
N
N
R1
R1
R1
X
X
X
Cl
Cl
4a-4d
N
N
3
R2
R2
-(CH2)4-
Ph
R3
R
X
NH
S
S
S
COOEt
NH2
5
a
b
4
a
b
c
d
R1
benzo
benzo
R3
H
S
4-BrC6H4
4-FC6H4
H
H
5a, 5b
(ii)
O
(iii)
R2
R1
R
N
X
N
R
NH
N
R3
N
X
or 7e-7g
S
R1
O
6a, 6b
7a-7g
O
R1
benzo NH
benzo
7
a
b
c
d
e
f
R
R1 R2
R3
X
NH
NH
S
S
S
R
X
6
a
b
benzo
-(CH2)4-
Ph
-(CH2)4-
benzo
benzo
benzo
H
S
Ph
H
-(CH2)4-
-(CH2)4-
4-BrC6H4
4-FC6H4
4-FC6H4
H
H
H
S
S
g
Ph
H
(i) ClCH2COCl, dioxane, 1 equivalent of pyridine
(ii) DMF, 2 equivalents of 5a, 5b, 100 oC
(iii) dioxane, 1 equivalent of 5a, 5b, 1 equivalent of Et3N, reflux
SCHEME 1
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368
Volovenko, Resnyanska, Tverdokhlebov:
m aterials, on ly tricyclic products of in tram olecular alkylation 6a, 6b were
isolated, wh ereas 4-arylth iazolyl derivatives 4c, 4d gave th e expected
pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin es 7e–7g. It sh ould be n oted th at th e
tran sform ation of ch loron itriles 4a, 4b in to com poun ds 6a, 6b on treat-
m en t with trieth ylam in e or oth er bases h as been reported previously12,14
.
Apparen tly, th e differen t beh avior of derivatives 4a, 4b an d 4c, 4d un der
alkalin e con dition s is explain ed in term s of steric factors. In th e case of
com poun ds 4c, 4d , th e substituen t R sh ields h eterocyclic n itrogen h in der-
in g in tram olecular alkylation . Such h in dran ce is absen t in com poun ds 4a,
4b an d th at facilitates th eir con version in to 6a, 6b in th e presen ce of tri-
eth ylam in e.
An attem pt to carry out th e discussed reaction with eth yl 5-acetyl-
2-am in o-4-m eth ylth ioph en e-3-carboxylate (5c, R2 = CH3, R3 = Ac) failed.
On ly startin g ch loron itriles 4a–4d were recovered after h eatin g with com -
poun d 5c in DMF for several h ours. Perh aps th e presen ce of an addition al
electron -with drawin g group, n am ely acetyl, decreases th e n ucleoph ilicity of
th e am in o group m akin g its alkylation im possible.
Th e structure of com poun ds 7a–7g was con firm ed by 1H NMR, IR data
an d elem en tal an alysis. 1H NMR spectra of tricycles 7a–7g recorded
in DMSO-d6 sh ow a two-proton sin glet at δ 4.5–4.8 ppm assign ed to th e
m eth ylen e group. A D2O-exch an gable broad sign al of th e NH group is ob-
served at δ 11.5–12.0 ppm . Th e proton sign als of substituen ts R, R1, R2, R3
appear at expected δ values. Th ere are n o sign als of th e eth oxy group in th e
1H NMR spectra of com poun ds 7. Th eir IR spectra revealed th e absen ce of
n itrile absorption in dicatin g clearly th e rin g closure with its participation .
At th e sam e tim e, stron g absorption was observed in th e 1 650–1 690 cm –1
region (two separate ban ds or occasion ally on e broad ban d). It was assign ed
to th e two carbon yls. Th e absen ce of both absorption above 1 700 cm –1 in
IR an d eth oxy group sign als in 1H NMR con firm s in corporation of th e ester
group in to pyrim idin e rin g. Hen ce th e spectral data an d elem en tal an alysis
are in good agreem en t with th e structure of 6-h etaryl-4,5,7,8-tetrah ydro-
pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin e-4,7-dion es 7a–7g.
In con clusion , th e presen t in vestigation h as resulted in preparation of th e
first exam ples of h etaryl-substituted pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin es.
Scope an d lim itation s of th e m eth od h ave been discussed. Th e ch loro-
n itriles 4 were sh own to be suitable precursors for th e syn th esis of h etaryl-
substituted h eterocyclic system s an d th e study of th eir syn th etic poten tial
is bein g con tin ued.
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Pyrrolo[1,2-a]thieno[3,2-e]pyrimidine Derivatives
369
EXPERIMENTAL
Gen eral
Meltin g poin ts were determ in ed in open capillary tubes on Th iele’s apparatus an d are un cor-
rected. IR spectra were obtain ed on a Pay Un icam SP 3-300 spectrom eter in KBr tablets.
1H NMR spectra were recorded on Bruker WP-100 SY (100 MHz) an d Varian VXR-300
(300 MHz) spectrom eters in DMSO-d6 solution (if n ot oth erwise stated) usin g TMS as in ter-
n al stan dard. 13C NMR spectra were recorded on Mercury 400 spectrom eter (100 MHz for
13C) in CF3CO2D solution . Ch em ical sh ifts are given in δ-scale (ppm ) down field from TMS
an d couplin g con stan ts J in Hz. Th e purity of all com poun ds prepared was ch ecked by TLC
on Silufol UV-254 plates with ch loroform –m eth an ol (9 : 1) as eluen t an d con firm ed by
1H NMR spectroscopy.
Solven ts an d Reagen ts
Com m ercial dioxan e was kept over sodium h ydroxide overn igh t, th en decan ted, refluxed
with sodium for on e day an d distilled. Com m ercial DMF was kept over P2O5 for 3–4 days
an d distilled un der reduced pressure. Com m ercial trieth ylam in e an d pyridin e were distilled
over sodium h ydroxide. Am in oth ioph en es 5a an d 5b were prepared accordin g to Gewald’s
m eth od10
. .
Ch loron itriles 4a –4c were obtain ed by previously described procedures12
2-Brom o-1-(4-fluoroph en yl)eth an -1-on e was prepared as reported15. Cyan oth ioacetam ide
an d ch loroacetyl ch loride are com m ercially available an d were used with out addition al puri-
fication .
2-[4-(4-Fluoroph en yl)th iazol-2-yl]aceton itrile (3d )
2-Brom o-1-(4-fluoroph en yl)eth an -1-on e (21.7 g, 0.1 m ol) was added quickly to a warm solu-
tion of cyan oth ioacetam ide (10 g, 0.1 m ol) in eth an ol (100 m l) an d th e resultin g m ixture
was h eated on a water bath for 2 h . After coolin g, th e precipitated crystals of 3d ·HBr were
filtered off an d suspen ded in con cen trated aqueous am m on ia for 1 h . Th e resulted crystals
were separated by suction an d dried to give an alytical pure 3d (7 g, 32%). Th e eth an olic
m oth er liquor was evaporated to dryn ess in vacuo an d th e residue was th orough ly triturated
with dilute aqueous am m on ia. Th e solid obtain ed was filtered off an d crystallized from eth a-
n ol to give an addition al portion of 3d (13 g, 60%). Th e overall yield is 92%. M.p. 64 °C.
For C11H7FN2S (218.3) calculated: 60.54% C, 3.23% H, 12.84% N, 14.69% S; foun d: 60.49% C,
3.28% H, 12.92% N, 14.74% S. IR: 2 215 (CN), 1 590, 1 490, 1 210 (CF), 835, 740. 1H NMR:
8.00 s, 1 H (S-CH=); 7.98 dd, 2 H, J(3′,2′) = 9.0, J(2′,F) = 3.3 (2′,6′-HFC ); 7.21 t, 2 H, J(3′,2′) =
6 H 4
J(3′,F) = 9.0 (3′,5′-HFC ); 4.53 s, 2 H (CH2).
6 H 4
4-Ch loro-2-[4-(4-fluoroph en yl)th iazol-2-yl]-3-oxobutan on itrile (4d )
Ch loroacetyl ch loride (2.4 m l, 0.03 m ol) was added portion wise with caution to a warm
(40–50 °C) solution of n itrile 3d (6.5 g, 0.03 m ol) an d pyridin e (2.5 m l, 0.0315 m ol) in
dioxan e (15 m l). Th e resultin g m ixture was h eated on a water bath for 1 h . After coolin g,
th e precipitated solid was filtered off, th orough ly wash ed with water an d dried to give 4d
(6.8 g, 77%). Th e substan ce obtain ed was sufficien tly pure for furth er use. An an alytical
sam ple of 4d was addition ally purified by recrystallization from dioxan e. M.p. 210 °C. For
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

370
Volovenko, Resnyanska, Tverdokhlebov:
C13H8ClFN2OS (294.7) calculated: 52.98% C, 2.74% H, 12.03% Cl, 9.50% N, 10.88% S;
foun d: 53.04% C, 2.70% H, 12.10% Cl, 9.41% N, 10.79% S. IR: 3 280 (NH), 2 180 (CN), 1 600,
1 490, 1 220 (CF), 765. 1H NMR: 12.02 br s, 1 H (NH); 7.80 dd, 2 H, J(3′,2′) = 8.7, J(2′,F) =
5.4 (2′,6′-HFC ); 7.45 s, 1 H (S-CH=); 7.27 t, 2 H, J(3′,F) = J(3′,2′) = 8.7 (3′,5′-HFC ); 4.24 s,
6 H 4
6 H 4
2 H (CH2).
6-Hetaryl-4,5,7,8-tetrah ydropyrrolo[1,2-a]th ien o[3,2-e]pyrim idin e-4,7-dion es (7a–7g).
Gen eral Procedure
Method A. Solution of ch loron itrile 4a –4d (0.003 m ol) an d am in oth ioph en e 5a , 5b
(0.006 m ol) in DMF (3 m l) was boiled for several m in utes to dissolve all startin g m aterials
an d th en h eated on a water bath for 3–4 h . After coolin g, th e form ed precipitate was filtered
off, wash ed successively with water an d m eth an ol an d dried at 100 °C un der reduced pres-
sure to give com poun ds 7a–7g. In m ost cases th e products were an alytically pure but, if
n eeded, th ey could be purified by recrystallization from DMF.
Method B. Solution of ch loron itrile 4a –4d (0.003 m ol), am in oth ioph en e 5a , 5b
(0.003 m ol) an d trieth ylam in e (0.4 m l, 0.003 m ol) in dioxan e (5 m l) was boiled for several
m in utes to dissolve all startin g m aterials an d th en h eated on a water bath for 3–4 h . After
coolin g th e m ixture was worked-up as in m eth od A. Wh en com poun ds 4c, 4d were used as
startin g m aterials, pyrrolo[1,2-a]th ien o[3,2-e]pyrim idin es 7e–7g were isolated. Startin g from
ch loron itriles 4a or 4b, 6-oxo-5,6-dih ydro-1H-ben zo[d]pyrrolo[1,2-a]im idazole-7-carbon itrile
(6a) an d 6-oxo-5,6-dih ydroben zo[d]pyrrolo[2,1-b]th iazole-7-carbon itrile (6b), respectively,
were obtain ed irrespective of th e am in oth ioph en e 5 used. Th e iden tity of com poun ds 6a, 6b
with previously described on es12,14 was proven by com parison with auth en tic sam ples (IR
spectra an d m ixed m eltin g poin ts).
3-(2-Benzoimidazolyl)-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e]pyrrolo[1,2-a]pyrimi-
dine-2,5-dione (7a). Yield 67% (m eth od A). M.p. > 300 °C. For C20H16N4O2S (376.4) calcu-
lated: 63.81% C, 4.28% H, 14.88% N, 8.52% S; foun d: 63.78% C, 4.21% H, 14.92% N,
8.59% S. IR: 3 200 (NH), 2 920, 1 665, 1 615, 1 570, 1 540, 1 455, 1 020, 960, 745. 1H NMR:
11.84 br s, 1 H (NH); 7.66 m , 2 H (HR,R1); 7.25 m , 2 H (HR,R1); 4.49 s, 2 H (1-H); 2.90 t, 2 H,
J(6,7) = 6.5 (6-H); 2.72 t, 2 H, J(9,8) = 7.0 (9-H); 1.79 m , 4 H (7,8-H). 13C NMR: 24.18 (7-C),
25.31 (8-C), 27.50 (9-C), 28.10 (6-C), 58.40 (1-C), 89.19 (3-C), 117.97 (5b-C), 119.67 (9a-C),
130.56 (5a-C), 132.51 (10a-C), 136.80 (5,6-CHet), 137.25 (4,7-CHet), 144.43 (3a,7a-CHet),
154.86 (3a-C), 160.04 (2-CHet), 163.08 (5-C), 192.99 (2-C).
6 -(Ben zoim ida zol-2 -yl)-3 -ph en yl-4 ,5 ,7 ,8 -tetra h ydropyrrolo[1 ,2 -a ]th ien o[3 ,2 -e]pyrim i-
dine-4,7-dione (7b). Yield 58% (m eth od A). M.p. > 300 °C. For C22H14N4O2S (398.5) calcu-
lated: 66.32% C, 3.54% H, 14.06% N, 8.05% S; foun d: 66.29% C, 3.55% H, 14.11% N,
7.98% S. IR: 3 200 (NH), 1 655 (CO), 1 620 (CO), 1 560, 1 540, 1 475, 1 440, 1 330, 1 170,
720. 1H NMR: 11.63 br s, 1 H (NH); 7.73 m , 2 H (HR,R1); 7.42 m , 7 H (HR2, HR,R1); 7.25 s, 1 H
(HR3); 4.74 s, 2 H (8-H).
3-(Benzothiazol-2-yl)-1,2,4,5,6,7,8,9-octahydro[1]benzothieno[3,2-e]pyrrolo[1,2-a]pyrimi-
dine-2,5-dione (7c). Yield 57% (m eth od A). M.p. > 300 °C. For C20H15N3O2S2 (393.5) calcu-
lated: 61.05% C, 3.84% H, 10.68% N, 16.30% S; foun d: 61.12% C, 3.82% H, 10.62% N,
16.28% S. IR: 2 930 (CH), 1 685 (CO), 1 665 (CO), 1 590, 1 540, 1 510, 1 185, 1 110, 950,
750. 1H NMR: 11.72 br s, 1 H (NH); 8.05 d, J(4′,5′) = 8.1, 1 H (4′-HR,R1); 7.97 d, 1 H, J(7′,6′) =
8.1 (7′-H R,R1); 7.49 t, 1 H, J(6′,5′) = J(6′,7′) = 8.1 (6′-H R,R1); 7.35 t, 1 H, J(5′,6′) = J(5′,4′) = 8.1
(5′-H R,R1); 4.61 s, 2 H (1-H); 2.91 m , 2 H (6-H); 2.75 m , 2 H (9-H); 1.82 m , 4 H (7,8-H).
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

Pyrrolo[1,2-a]thieno[3,2-e]pyrimidine Derivatives
371
13C NMR: 28.35 (7-C), 29.35 (8-C), 31.78 (9-C), 32.20 (6-C), 63.01 (1-C), 101.01 (3-C),
122.98 (5b-C), 123.22 (9a-C), 123.45 (5a-C), 129.82 (10a-C), 133.81 (6-CHet), 134.80 (5-CHet),
136.98 (7-CHet), 139.74 (4-CHet), 142.03 (7a-CHet), 144.99 (3a-CHet), 160.63 (3a-C), 165.89
(2-CHet), 170.25 (5-C), 195.85 (2-C).
6-(Benzothiazol-2-yl)-3-phenyl-4,5,7,8-tetrahydropyrrolo[1,2-a]thieno[3,2-e]pyrimidine-4,7-dione
(7d ). Yield 49% (m eth od A). M.p. > 300 °C. For C22H13N3O2S2 (415.5) calculated: 63.60% C,
3.15% H, 10.11% N, 15.43% S; foun d: 63.64% C, 3.09% H, 10.16% N, 15.48% S. IR: 3 215
(NH), 1 690 (CO), 1 670 (CO), 1 600, 1 545, 1 510, 1 080, 955, 750, 715. 1H NMR: 11.52 br s,
1 H (NH); 7.96 m , 2 H (HR,R1); 7.45 m , 7 H (HR2, HR,R1); 7.21 s, 1 H (HR3); 4.63 s, 2 H (8-H).
3-[4-(4-Bromophenyl)thiazol-2-yl]-1,2,4,5,6,7,8,9-octahydro[1]benzothieno[3,2-e]pyrrolo-
[1,2-a]pyrimidine-2,5-dione (7e). Yields 52% (m eth od A) an d 56% (m eth od B). M.p. > 300 °C.
For C22H16BrN3O2S2 (498.4) calculated: 53.02% C, 3.24% H, 16.03% Br, 8.43% N, 12.87% S;
foun d: 53.08% C, 3.19% H, 16.11% Br, 8.38% N, 12.95% S. IR: 3 200 (NH), 2 920 (CH),
1 665 (CO), 1 595, 1 560, 1 505, 1 175, 1 120, 1 060, 1 000, 950, 825, 775. 1H NMR:
11.95 br s, 1 H (NH); 7.89 d, 2 H, J(3′,2′) = 9.0 (3′,5′-HR); 7.85 s, 1 H (HR1); 7.65 d, 2 H,
J(3′,2′) = 9.0 (2′,6′-HR); 4.51 s, 2 H (1-H); 2.80 m , 4 H (6,9-H); 1.79 m , 4 H (7,8-H).
3-[4-(4-Fluorophenyl)thia zol-2-yl]-1,2,4,5,6,7,8,9-octa hydro[1]benzothieno[3,2-e]pyrrolo-
[1,2-a]pyrimidine-2,5-dione (7f). Yields 45% (m eth od A) an d 50% (m eth od B). M.p. > 300 °C.
For C22H16FN3O2S2 (437.5) calculated: 60.40% C, 3.69% H, 9.60% N, 14.66% S; foun d:
60.47% C, 3.74% H, 9.57% N, 14.71% S. IR: 3 200 (NH), 2 920 (CH), 1 670 (CO), 1 660
(CO), 1 580, 1 200 (CF), 920, 835, 740. 1H NMR (CF3CO2D): 7.75 dd, 2 H, J(2′3′) = 8.4,
J(2′,F) = 3.7 (2′,6′-HR); 7.58 s, 1 H (HR1); 7.31 t, 2 H, J(3′,2′) = J(3′,F) = 8.4 (3′,5′-HR); 5.05 s,
2 H (1-H); 3.09 m , 2 H (6-H); 2.91 m , 2 H (9-H); 2.02 m , 4 H (7,8-H). 13C NMR: 23.46 (7-C),
24.48 (8-C), 26.79 (9-C), 27.35 (6-C), 57.68 (1-C), 95.61 (3-C), 112.02 (1′-CR), 118.59 (5b-C),
119.18 (9a-C), 119,95 (5a-C), 125.16 (10a-C), 130.81 (3′,5′-CR), 135.06 (2′,6′-CR), 136.77
(5-CHet), 145.66 (4-CHet), 155.34 (2-CHet), 160.56 (3a-C), 165.36 d, JCF = 145 (4′-CR,), 168.58
(5-C), 190.59 (2-C).
6-[4-(4-Fluorophenyl)thiazol-2-yl]-3-phenyl-4,5,7,8-tetrahydropyrrolo[1,2-a]thieno[3,2-e]pyrimi-
dine-4,7-dione (7g). Yields 42% (m eth od A) an d 46% (m eth od B). M.p. 259 °C. For
C
24H14FN3O2S2 (459.5) calculated: 62.73% C, 3.07% H, 9.14% N, 13.96% S; foun d:
62.68% C, 3.15% H, 9.10% N, 14.01% S. IR: 3 215 (NH), 1 680 (CO), 1 660 (CO), 1 606,
1 210 (CF), 865, 740. 1H NMR (CF3CO2D): 8.00 dd, 2 H, J(3′,2′) = 9.2, J(2′,F) = 3.3 (2′,6′-HR);
7.75 s, 1 H (R1); 7.38 m , 5 H (HR2); 7.24 t, 2 H, J(3′,2′) = J(3′,F) = 9.2 (3′,5′-HR); 7.20 s, 1 H
(R3); 4.58 s, 2 H (8-H).
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