S. R. Donohue, R. F. Dannals / Tetrahedron Letters 50 (2009) 7271–7273
7273
aryl fluoride.19 A variation of this method has been reported, in
which, the decomposition to aryl fluoride is carried out photo-
chemically.20 In the second method, the aryl amine is converted
to the aryl fluoride in one-pot by diazotization in 70% HF–pyridine
in high-yield.21 This was the method of choice for the final step
(Scheme 5). Recently, a method for the preparation of truly anhy-
drous fluoride ion has been established.22 Since 2 is susceptible
to SNAr reaction by activated fluoride ion, as in radiolabeling con-
ditions, this represents an attractive pathway for the synthesis 1
without use of Balz-Schiemann reaction.
O
O
N
N
a or b
Br
O
O
NO2
O
9
3. Conclusion
8
In conclusion, we have developed a unique synthesis of 1 and its
cognates that allows for increased SAR development within the
imidazobenzodiazapine platform. Furthermore this novel pathway
allows for the synthesis of precursor for 18F-labeling and reference
compound in the same process. This newly developed synthetic
pathway should aid in the development of 18F-labeled GABAA-Bz
site radioligands with enhanced in vivo properties.
O
N
Br
N
a or c
O
O
Acknowledgment
NO2
10
This work was supported in part by the Division of Nuclear
Medicine of Johns Hopkins School of Medicine.
Scheme 3. Syntheses of
9 and 10. Reagents, conditions, and yields: (a) NBS,
benzene, benzoyl peroxide(cat), reflux; (b) NBS, benzene, benzoyl peroxide(cat), h
m
(60 W), 86%; (d) NBS, MeCN, benzoyl peroxide(cat), reflux, 41%.
Supplementary data
Supplementary data (experimental details of chemistry and
compound characterization) associated with this article can be
O
O
N
References and notes
a
N
N
9
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O
NO2
2
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Scheme 4. Synthesis of 2. Reagents, conditions, and yields: (a) MeOH, DIEPA,
MeNH2, reflux, 64% (from 9), 61% (from 8 without isolating 9).
O
O
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O
O
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N
N
N
N
N
N
a
b
2
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O
O
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F
NH2
1
11
Scheme 5. Syntheses of 11 and 1. Reagents, conditions and yields: (a) aq-TiCl3,
MeOH, rt, 83%; (b) NaNO2, 70% HF–pyridine, rt for 1 h, 100 °C for 1 h, 51%.
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amine is diazotized with sodium nitrite in the presence of fluoro-
boric acid. The resulting diazonium fluoroborate precipitate is iso-
lated and then thermally decomposed at high temperature to give
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