Solid phase synthesis of 2-aminobenzothiazoles

Article abstract of DOI:10.1016/j.bmcl.2009.11.055

A traceless solid supported protocol for the synthesis of 2-aminobenzothiazoles is described, employing resin-bound acyl-isothiocyanate and a series of anilines. Cyclization of the resulting N-acyl, N′-phenyl-thioureas generates the 2-aminobenzothiazole scaffold, which can be further elaborated prior to hydrazine-mediated cleavage of the final products from the carboxy-polystyrene resin. A small, focused library of 2-aminobenzothiazoles was prepared.

Full text of DOI:10.1016/j.bmcl.2009.11.055

Bioorganic & Medicinal Chemistry Letters 20 (2010) 644–648
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Bioorganic & Medicinal Chemistry Letters
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Solid phase synthesis of 2-aminobenzothiazoles
a
Francesco Piscitelli a, Carlo Ballatore a,b, , Amos B. Smith III
*
a Department of Chemistry, University of Pennsylvania, 231 South 34th St., Philadelphia, PA 19104-6323, United States
b Department of Pathology & Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104-6323, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A traceless solid supported protocol for the synthesis of 2-aminobenzothiazoles is described, employing
resin-bound acyl-isothiocyanate and a series of anilines. Cyclization of the resulting N-acyl, N0-phenyl-
thioureas generates the 2-aminobenzothiazole scaffold, which can be further elaborated prior to hydra-
zine-mediated cleavage of the final products from the carboxy-polystyrene resin. A small, focused library
of 2-aminobenzothiazoles was prepared.
Received 12 October 2009
Revised 11 November 2009
Accepted 16 November 2009
Available online 1 December 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Libraries of compounds based on diverse heterocyclic scaffolds
comprise a key aspect of modern drug discovery. In this context,
solid supported synthesis has proved to be a powerful tool leading
to a wide-range of heterocyclic compounds.1 However, to the best
of our knowledge, a procedure for the solid phase synthesis of 2-
aminobenzothiazoles has not been reported. The 2-aminobenzo-
thiazole scaffold is one of the ‘privileged’ structures in medicinal
chemistry.2 Indeed, various examples featuring this particular scaf-
fold have been prepared, many exhibiting remarkable biological
activities.3,4 Given the importance of this particular chemical entity
to the field of medicinal chemistry, the development of improved
and/or alternative methods for the rapid construction of libraries
of derivatives is desirable. Although examples of solid supported
synthesis of benzothiazoles have been reported,5,6 these methods
are not applicable to 2-aminobenzothiazoles. We thus undertook
a focused study to adapt previously disclosed methods for solution
phase synthesis to the solid phase for this particular class of
heterocycles.
The now classical synthesis of 6-substituted 2-aminobenzo-
thiazoles entails treatment of 4-substituted anilines with potas-
sium thiocyanate in the presence of bromine in acetic acid
(Scheme 1A).7 This method, however, is not generally applicable
as thiocyanation in the para position of anilines is often the pre-
dominant reaction when 4-unsubstituted anilines are employed
under these or similar oxidation conditions (Scheme 1B).8,9 Alter-
native methods for the syntheses of 4, 5, 6, and 7 substituted 2-
aminobenzothiazoles employ phenylthioureas as the synthetic
precursors (Scheme 1C). In these cases, heterocycle ring formation
can be carried out, albeit non regioselectively, by treating the
phenylthioureas with bromine in chloroform10 or acetic acid.11
Alternatively, regiospecific cyclizations can be performed via SNAri
reactions, employing phenylthioureas obtained from the appropri-
ate ortho-fluoroanilines in the presence of sodium methoxide.12
We report here adaptation of these reaction conditions onto solid
support beginning with resin-bound isothiocyanate.
The resin-bound isothiocyanate 3 was prepared as previously
described in two steps from carboxy-polystyrene (Scheme 2).13
Conversion of 3 to the N-acyl, N0-phenylthioureas of general struc-
ture 4 was then readily achieved upon treatment of 3 with the
appropriate aniline at room temperature in N,N-dimethylformam-
ide.14 This reaction can be conveniently monitored by infrared
spectroscopy following the disappearance of the characteristic iso-
X
X
S
N
KSCN
NH2
(A
)
)
Br2, AcOH
NH2
S
H
KSCN
N
S
(B
Br2, AcOH
NH2
NH2
X
X
O
H
H
S
O
R
N
C
(C)
NH2
N
N
R
X
X
H
H
1) cyclization
2) deprotection
H
S
N
NH2
X
Scheme 1. Commonly employed methods for the solution phase synthesis of 2-
aminobenzothiazoles (A and C); thiocyanation of 4-unsubstituted anilines upon
treatment with potassium thiocyanate in the presence of bromine in acetic acid (B).
* Corresponding author.
E-mail address: bcarlo@sas.upenn.edu (C. Ballatore).
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.11.055

F. Piscitelli et al. / Bioorg. Med. Chem. Lett. 20 (2010) 644–648
645
O
O
O
c
a
b
N
OH
Cl
C
S
1
2
3
R
R
O
S
X
7
4
1
O
S
S
6
R
N
N
e
NH2
d
H
N
N
H
2
H
N
5
3
X = H, F, Br
4
5
6
Scheme 2. Reagents and conditions: (a) oxalyl chloride, DCE, rt, 16 h; (b) Bu4NNCS, DCE/THF, rt, 16 h; (c) aniline, DMF, rt, 16 h; (d) For X = H, Method A: Br2 (6 equiv), acetic
acid, rt, 16 h; for X = F, Method B: NaH (6 equiv), DMF, rt, 16 h; for X = Br, Method C: NaH (10 equiv), DMF, 100 °C, 16 h (e) hydrazine monohydrate, EtOH, 150 °C, MW, 30 min.
thiocyanate band at ꢀ1910 cmꢁ1 (Fig. 1). When X = H cyclization of
4 to 2-acylaminobenzothiazole 5 was then performed by treatment
with six equivalents of bromine in acetic acid (Scheme 2, Method
Finally, the desired 2-aminobenzothiazoles of general structure
6 were obtained in good overall yield and >85% purity upon treat-
ment of 5 with 4% hydrazine monohydrate in ethanol (Table 1).14
Alternative TFA-mediated cleavage conditions were also investi-
gated, however, the optimized hydrazine cleavage conditions
proved more reliable, and generally proceeded with little or no
trace of contaminants or by-products (cf., Fig. 2).
A
14). Alternatively, when X = F or Br, benzothiazoles obtained
(e.g., entries e and h, Table 1), were formed by treatment of the cor-
responding N-acyl, N0-phenylthioureas with sodium hydride
(Methods B and C14) via an SNAri mechanism.
Figure 1. IR spectra.

646
F. Piscitelli et al. / Bioorg. Med. Chem. Lett. 20 (2010) 644–648
Figure 2. LC/MS analysis of the crude reaction obtained after hydrazine-mediated cleavage (Table 1, entry f); A: photodiode array detector; B: total ion current; C: mass
spectrum.
As anticipated, when 3-substituted anilines (e.g., entries c and f,
Table 1) were employed, oxidative cyclization conditions (Method
A) led to mixtures of two regioisomers (i.e., 5- and 7-substituted
2-aminobenzothiazoles); the relative ratio apparently determined
by the steric encumbrance of the substituent in the meta position
of the starting aniline. Thus, while 3-bromoaniline furnished a sep-
arable 1:1 mixture of 5- and 7-bromo-2-aminobenzothiazoles, un-
der the above reaction conditions, the 3-phenylaniline generated a
mixture (95:5) in favor of the 5-substituted-2-amino-benzothiazole
(cf., entries c and f, Table 1), which could be readily separated and
purified by column chromatography or crystallization. Single crystal
X-ray analysis confirmed the structure of 6f (Fig. 3).
Although mixtures of regioisomers are often acceptable in the
generation of libraries for HTS, single isomers could be obtained
Figure 3. X-ray crystal structure of compound 6f (CCDC 753930).

F. Piscitelli et al. / Bioorg. Med. Chem. Lett. 20 (2010) 644–648
647
Table 1
Representative examples of 2-aminobenzothiazoles prepared
Table 3
Cross-coupling reaction investigation
Entry Method Aniline
Product 6
Yielda
(%)
Entry Conditions
Conversiona
(%)
Suzuki coupling (from 5c to 7):
Br
S
N
NH2
NH2
i
PhB(OH)2, (5.0 equiv), K3PO4 (5.0 equiv), Pd(OAc)2
0
NH2
NH2
a
A
A
63
61
(0.1 equiv), DMF–H2O (9:1), MW, 150 °C, 15 min
PhB(OH)2, (5.0 equiv), K3PO4 (5.0 equiv), Pd(PPh3)4
(0.1 equiv), DMF–H2O (9:1), MW, 150 °C, 30 min
j
100
Br
Cl
Cl
Buchwald–Hartwig amination (from 5h to 8):
S
k
t-BuONa (10 equiv), morpholine (5 equiv), Pd2dba3
(0.05 equiv), BINAP (0.4 equiv), toluene, 90 °C, 24 h
t-BuONa (10 equiv), morpholine (5 equiv), Pd2dba3
(0.05 equiv), XPhos (0.4 equiv), toluene, 90 °C, 24 h.
t-BuONa (10 equiv), morpholine (5 equiv), Pd2dba3
(0.05 equiv), XPhos (0.4 equiv), DMF, 160 °C, MW, 1 h.
t-BuONa (10 equiv), morpholine (5 equiv), Pd(PPh3)4
(0.05 equiv), XPhos (0.4 equiv), DMF, 160 °C, MW, 1 h
40
50
b
N
l
Cl
Cl
Br
NH2
NH2
S
c
A
A
73*
68
m
n
50
NH2
NH2
Br
Br
N
100
S
d
N
Br
aConversion of the starting material by LC–MS analysis after cleavage of the
product.
NH2
F
Cl
S
e
f
B
A
41
NH2
Finally, in order to exemplify the utility of this synthetic proto-
col for the construction of libraries of 2-aminobenzothiazole
derivatives, we evaluated representative resin-bound bromobenzo
thiazoles 5c and 5h as possible starting points for further structural
elaboration. Thus, 5c and 5h were treated under either Suzuki15 or
Buchwald–Hartwig16 conditions to yield products of cross-cou-
pling. Representative examples of C–C, and C–N bond forming
reactions are summarized in Table 2.
Both cross-coupling reactions were carried out under micro-
wave promoted conditions. For these reactions, 0.05–0.1 mol % of
Pd(PPh3)4 was found to be the preferred catalyst (cf., Table 3).
In summary, we have developed an effective method for the so-
lid supported synthesis of 2-aminobenzo-thiazoles, with an
application to the preparation of a focused library of 2-aminoben-
zothiazole derivatives.
N
Cl
S
NH2
NH2
74**
N
Br
Br
S
NH2
NH2
NH2
g
A
C
53
70
N
Br
Br
Br
S
N
NH2
Br
h
Br
a
Overall yield after purification.
*
Approximately a 50:50 mixture of 5- and 7-bromo-2-aminobenzo-thiazoles.
Approximately a 95:5 mixture of 5- and 7-phenyl-2-aminobenzothiazole.
**
Acknowledgment
Financial support for this work was provided in part by the Uni-
versity of Pennsylvania Institute on Aging (IOA Pilot Research
Grant).
Table 2
Representative examples of cross-coupling reactions
References and notes
Conditions
Product
Yield
1. Gil, C.; Brase, S. J. Comb. Chem. 2008, 11, 175.
S
N
1) Suzuki
34% of 5-
Phenyl
30% of 7-
Phenyl
2. Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter,
W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S. J. Med. Chem. 2002, 31, 2235.
3. Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J. C.; Boireau, A.; Bour, Y.;
Coleno, M. A.; Doble, A.; Doerflinger, G.; Huu, C. D.; Donat, M. H.; Duchesne, J.
M.; Ganil, P.; Gueremy, C.; Honor, E.; Just, B.; Kerphirique, R.; Gontier, S.;
Hubert, P.; Laduron, P. M.; Le Blevec, J.; Meunier, M.; Miquet, J. M.; Nemecek, C.;
Mignani, S., et al J. Med. Chem. 1999, 42, 2828.
4. Young, R. C.; Mitchell, R. C.; Brown, T. H.; Ganellin, C. R.; Griffiths, R.; Jones, M.;
Rana, K. K.; Saunders, D.; Smith, I. R.; Sore, N. E., et al J. Med. Chem. 1988, 31,
656.
cross-coupling
NH2
NH2
5c*
5h
2) Cleavage
7
8
S
N
1) Buchwald-Hartwig
amination
N
2) Cleavage
40%
52%
O
5. Lim, H. J.; Myung, D.; Lee, I. Y.; Jung, M. H. J. Comb. Chem. 2008, 10, 501.
6. Mourtas, S.; Gatos, D.; Barlos, K. Tetrahedron Lett. 2001, 42, 2201.
7. Kaufmann, H. P. Arch. Pharm. 1928, 266, 197.
1) Buchwald-Hartwig
amination
8. Bhalerao, D. S.; Akamanchi, K. G. Synlett 2007, 2952.
S
N
9. Wu, G.; Liu, Q.; Shen, Y.; Wu, W.; Wu, L. Tetrahedron Lett. 2005, 46, 5831.
10. Sprague, K. M.; Land, A. H. In Heterocyclic Compounds; Elderfield, R. C., Ed.;
Wiley: New York, 1989; pp 582–587.
11. Sarkis, G. Y.; Faisal, E. D. J. Heterocycl. Chem. 1985, 22, 725.
12. Sedlak, M.; Hanusek, J.; Holcapek, M.; Sterba, V. J. Phys. Org. Chem. 2001, 14,
187.
2) Cleavage
NH2
5h
N
H
9
*
13. Wilson, L. J. Org. Lett. 2001, 3, 585.
Approximately
a 50:50 mixture of 5- and 7-phenyl-2-aminobenzo-thiazoles
14. Experimental procedures and characterization of compounds: General
procedure to prepare derivatives 4: A mixture of solid phase 3 (theoretical
load: 0.96 mmol/g, 200 mg, 0.19 mmol) and aniline (0.48 mmol) in N,N-
dimethylformamide (1.5 mL) was stirred at room temperature overnight. The
solid phase was filtered, washed with N,N-dimethylformamide, acetone, and
methanol (ꢂ3).General procedures to prepare derivatives 5: Method A:
cyclization with bromine. Bromine (150 mg, 0.05 mL, 0.96 mmol) was added
to mixture of solid phase 4 (X = H, theoretical load: 0.82 mmol/g, 200 mg,
(separable).
when ring formation was performed via SNAri, as exemplified by
entries e (Method B) and h (Method C); each proceeded regiospe-
cifically to furnish the 7-chloro- and the 5-bromo-2-aminobenzo-
thiazole 6e and 6h (Table 1), respectively.

648
F. Piscitelli et al. / Bioorg. Med. Chem. Lett. 20 (2010) 644–648
0.16 mmol) in acetic acid (1.5 mL). The reaction mixture was stirred at room
1H). 13C NMR (CDCl3): d 114.7, 119.6, 124.5, 125.8, 129.0, 151.5, 166.8 ppm. IR:
3402, 3264, 1602 cmꢁ1 HRMS: calcd for C7H6BrN2S+ 228.9435 found
temperature overnight. The solid phase was filtered, washed with water, N,N-
dimethylformamide and methanol (ꢂ3).Method B: cyclization with NaH (X = F).
NaH (60% wt. oil mineral dispersion, 40 mg, 0.96 mmol) was added to a
mixture of solid phase 4 (theoretical load: 0.84 mmol/g, 200 mg, 0.17 mmol) in
anhydrous N,N-dimethylformamide (1.5 mL). The reaction mixture was stirred
at room temperature overnight. Water (0.5 mL) was added, and the solid phase
was filtered and washed with water and methanol (ꢂ3).Method C: cyclization
with NaH (X = Br). NaH (60% wt. oil mineral dispersion, 60 mg, 1.54 mmol) was
added to a mixture of solid phase 4 (theoretical load: 0.77 mmol/g, 200 mg,
0.15 mmol) in anhydrous N,N-dimethylformamide (1 mL). The reaction
mixture was heated to 100 °C and stirred overnight. After cooling, water
(0.5 mL) was added, and the solid phase was filtered and washed with water
and methanol (ꢂ3).Suzuki coupling: A mixture of solid phase 5c (theoretical
load: 0.82 mmol/g, 200 mg, 0.16 mmol), phenylboronic acid (100 mg,
0.82 mmol), potassium phosphate (170 mg, 0.82 mmol) and tetrakis
(triphenylphosphine)palladium (20 mg, 0.1 mol%) in N,N-dimethylformamide
(1.8 mL) and water (0.2 mL) was heated to 150 °C using microwave irradiation
for 30 min. After cooling, the solid phase was filtered, washed with N,N-
dimethylformamide, dichloromethane and methanol (ꢂ3).Buchwald–Hartwig
amination: A dry microwave vessel was charged with the solid phase 5h
(theoretical load: 0.82 mmol/g, 200 mg, 0.16 mmol), the appropriate amine
m
.
228.9432.2-Amino-6-bromobenzothiazole (6d): White solid. Yield: 68%. All
data are in agreement with literature.182-Amino-7-chlorobenzothiazole (6e):
White solid. Yield: 41%, mp 177–178 °C (from ethanol) (Lit.1 169–170 °C). 1H
NMR (CDCl3): d 5.32 (br d s, 2H), 7.13 (dd, J = 1.0 and 8.0 Hz, 1H), 7.26 (t,
J = 8.0 Hz, 1H), 7.44 ppm (dd, J = 1.0 and 8.0 Hz, 1H). 13C NMR (MeOD): d 114.4,
119.5, 124.1, 125.2, 128.9, 151.5, 166.8 ppm. IR:
m 3395, 3262, 1633,
1535 cmꢁ1. HRMS: calcd for C7H6ClN2S+ 184.9940 found 184.9933.2-Amino-
5-phenylbenzothiazole (6f): White solid. Yield: 74% method A, (34% from Suzuki
coupling), mp 168–170 °C (from ethanol). 1H NMR (CD3OD): d 7.33–7.37 (m,
2H), 7.46 (t, J = 7.7 Hz, 2H), 7.63–7.66 ppm (m, 4H). 13C NMR (CD3OD): d 118.0,
118.4, 121.1, 121.9, 122.5, 126.7, 127.4, 127.8, 128.1, 128.9, 152.3 ppm. IR:
m
3423, 3230, 1613, 1523 cmꢁ1. HRMS: calcd for C13H11N2S+ 227.0643 found
227.0648.2-Amino-4,7-dibromobenzothiazole (6g): White solid. Yield: 53%, mp
266–267 °C (from ethanol). 1H NMR (DMSO-d6): d 7.12 (d, J = 8.3 Hz, 1H), 7.39
(d, J = 8.3 Hz, 1H), 8.09 ppm (br s, 2H). 13C NMR (DMSO-d6): d 109.9, 112.1,
124.9, 130.6, 134.0, 151.2, 166.7 ppm. IR:
m .
3470, 3177, 1634, 1530 cmꢁ1
HRMS: calcd for C7H5Br2N2S+ 306.8533, found 306.8540.2-Amino-5-
bromobenzothiazole (6h): White solid. Yield: 70% using the method C, 38%
using method A, mp 195–197 °C (from ethanol) (Lit.17 196–198 °C). 1H NMR
(MeOD): d 7.21 (dd, J = 1.8 and 8.3 Hz, 1H), 7.51–7.53 ppm (m, 2H). 13C NMR
(0.82 mmol),
XPhos
(31 mg,
0.07 mmol),
tetrakis
(triphenylphos
(MeOD): d 117.4, 118.8, 120.4, 122.6, 128.4, 151.9, 168.2 ppm. IR: m 3409, 3270,
phine)palladium (10 mg, 0.05 mol%), and sodium t-butoxide (160 mg,
1.64 mmol). Degassed and dry N,N-dimethylformamide (2 mL) was added,
and the resulting mixture was heated to 150 °C using microwave irradiation
for 1 h. After cooling, the solid phase was filtered, washed with N,N-
dimethylformamide,
Hydrazine monohydrate (80 mg, 0.08 mL, 1.64 mmol) was added to
1642, 1529 cmꢁ1. HRMS: calcd for C7H6BrN2S+ 228.9435 found 228.9531.2-
Amino-7-phenylbenzothiazole (7): White solid. Yield: 30% from Suzuki coupling,
mp 156–158 °C (from ethanol). 1H NMR (CD3OD): d 7.16 (dd, J = 2.0 and 7.6 Hz,
1H), 7.36–7.44 (m, 3H), 7.50 (t, J = 7.6 Hz, 2H), 7.63–7.65 ppm (m, 2H). 13C NMR
(CD3OD): d 117.8, 121.3, 126.8, 127.9, 128.5, 121.4, 129.5, 135.2, 141.2, 154.2,
dichloromethane
and
methanol
(ꢂ3).Cleavage:
a
167.0. ppm. IR: m . HRMS: calcd for
3451, 3296, 3135, 1621, 1531 cmꢁ1
mixture of the solid phase 5 and ethanol (1.9 mL). The reaction mixture was
heated to 150 °C using microwave irradiation for 30 min. After cooling the
resin was filtered and washed with ethyl acetate and methanol (ꢂ3). The
solvent was evaporated and the residue was purified by silica gel column
chromatography (using ethyl acetate–n-hexane 2:3 as eluent) or by
crystallization from the appropriate solvent to give the desired title
compound.2-Amino-4-bromobenzothiazole (6a): White solid. Yield: 63%, mp
182–184 °C (from ethanol) (Lit.17 183–184 °C). 1H NMR (DMSO-d6): d 6.91 (t,
J = 7.7 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.85 ppm (br s,
2H). 13C NMR (DMSO-d6): d 110.9, 121.0, 122.5, 129.2, 132.1, 151.3, 167.6 ppm.
C13H11N2S+ 227.0643 found 227.0647.N6-(Naphthalen-1-yl)benzo[d]thiazole-
2,6-diamine (9): White solid. Yield: 63%, mp 231–133 °C (from ethanol). 1H
NMR (CD3OD): d 6.86 (dd, J = 1.1 and 7.9 Hz, 1H), 7.06 (d, J = 1.1 Hz, 1H), 7.34–
7.54 (m, 9H), 7.86 (d, J = 7.8 Hz, 1H), 8.15 ppm (d, J = 7.9 Hz, 1H). 13C NMR
(CD3OD): d 105.1, 111.3, 113.6, 119.1, 119.2, 119.8, 120.4, 120.8, 121.0, 123.4,
124.2, 124.3, 126.5, 126.6, 133.6, 151.3, 159.1 ppm. IR:
m 3401, 3348, 3155,
1629, 1605, 1551 cmꢁ1 HRMS: calcd for C17H14N3S+ 292.0908 found
.
292.0905.2-Amino-5-(4-morpholyl)benzothiazole (8): White solid. Yield 40%,
mp 213–215 °C (from ethanol). 1H NMR (DMSO-d6): d 2.32 (t, J = 4.7 Hz, 4H),
3.03 (t, J = 4.7 Hz, 4H), 5.98 (dd, J = 1.0 and 8.1 Hz, 1H), 6.18 (d, J = 1.0 Hz, 1H),
6.61 ppm (d, J = 8.1 Hz, 1H). 13C NMR (MeOD): d 48.8, 65.3, 103.9, 110.2, 119.2,
IR:
m
3450, 3272, 1632, 1530 cmꢁ1. HRMS: calcd for C7H5BrN2S+ 228.9401
found 228.9404.2-Amino-4,7-dichlorobenzothiazole (6b): White solid. Yield:
61%, mp 228–230 °C (from ethanol). 1H NMR (DMSO-d6): d 7.08 (d, J = 8.5 Hz,
1H), 7.32 (d, J = 8.5 Hz, 1H), 8.12 ppm (br s, 2H). 13C NMR (DMSO-d6): d 120.6,
120.6, 149.4, 151.4, 167.9 ppm. IR: m .
3410, 3340, 3170, 1633, 1615, 1545 cmꢁ1
HRMS: calcd for C11H14N3OS+ 236.0858 found 236.0853.
15. Miyaura, N.; Suzuki, A. Chem. Rev. 2002, 95, 2457.
121.6, 127.9, 129.4, 131.9, 150.5, 167.7 ppm. IR:
m
3399, 3246, 1624,
16. Cross-Coupling Reactions; Muci, A., Buchwald, S., Eds.; Springer: Berlin/
Heidelberg, 2002; pp 131–209.
17. Jackson, F. H.; Peters, Arnold T. J. Chem. Soc., Sect C 1969, 2, 268.
18. Rana, A.; Siddiqui, N.; Khan, S. A.; Ehtaishamul, S. H.; Bhat, M. A. Eur. J. Med.
Chem. 2008, 43, 1114.
1556 cmꢁ1. HRMS: calcd for C7H5Cl2N2S+ 218.9551 found 218.9557.2-Amino-
7-bromobenzothiazole (6c): White solid. Yield: 35%, mp 189–191 °C (from
ethanol) (Lit.17 196–197 °C). 1H NMR (CDCl3):
d
5.24 (br s, 2H), 7.20 (t,
J = 7.9 Hz, 1H), 7.26 (dd, J = 1.0 and 7.9 Hz, 1H), 7.48 ppm (dd, J = 1.0 and 7.9 Hz,