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R. M. Feeny et al.
LETTER
solvent for 3 min, 40–95% organic solvent over 15 min,
(60% in paraffin, 1.5 equiv) was added in portions.
Phenylisothiocyanate (1 equiv) was added, the reaction
mixture was heated in a 45 °C oil bath, and the reaction was
monitored by TLC. The reaction mixture was cooled to room
temperature and then cooled in an ice–water bath. To this
reaction mixture was added a 0.5 M solution of HBr (5
equiv) in THF (made using 5.1 M HBr in acetic acid),
followed by the addition of hydrogen peroxide (3.5 equiv,
30% H2O2 solution). The reaction was stirred overnight and
filtered, after which, the solid was dissolved in CH2Cl2 (10
mL) and washed with sat. Na2CO3 (10 mL). The organic
layer was removed and the aqueous layer was washed with a
second portion of CH2Cl2 (10 mL). The combined CH2Cl2
solution was dried with anhydrous MgSO4, filtered and
concentrated in vacuo. The solid was dissolved in CH2Cl2 to
make a 0.05 M solution, which was cooled in an ice bath
under nitrogen. To this solution was added triethylamine
(7.2 equiv based on the crude weight of the filtered solid),
followed by dropwise addition of a 0.75 M solution of
methanesulfonyl chloride (1.5 equiv based on the crude
weight of the filtered solid) in CH2Cl2. After stirring the
reaction for 1 h, the reaction was diluted with CH2Cl2 and
washed twice with H2O. The organic layer was dried with
anhydrous MgSO4, filtered and concentrated in vacuo.
The residue was purified by silica chromatography (ethyl
acetate–n-hexane, 95% or CH2Cl2–n-hexane, 95%). The
purity of the product was confirmed by HPLC analysis using
two different conditions with a C18, 5 mm (250 × 4.6 mm)
column at 40 °C, and monitored at 220 nm.
95% organic solvent for 2 min at 1.0 mL/min. The retention
time of the product under conditions A was 13.6 min (>99%
purity) and under conditions B it was 15.8 min (>99%
purity).
(9) For procedures see the Supporting Information.
(10) Compound 6c: 1H NMR (400 MHz, CDCl3): d = 2.27 (s,
3 H), 2.32 (s, 3 H), 6.77–7.32 (m, 13 H). 13C NMR (100
MHz, CDCl3): d = 21.0, 21.2, 46.4, 126.3, 127.4, 128.9,
129.1, 129.1, 129.3, 130.0, 132.0, 136.3, 137.5, 141.7,
142.3, 161.5, 188.2. HRMS (ESI+): m/z [M + H]+ calcd for
C23H22N3O2S3: 468.0859; found: 468.0857. The purity of the
product was confirmed by HPLC using the same two
conditions used for 6b. The retention time of the product
under conditions A was 14.1 min (98% purity) and under
conditions B was 16.5 min (>99% purity).
Compound 6d: 1H NMR (400 MHz, CDCl3): d = 2.65–2.80
(m, 2 H), 3.12–3.33 (m, 2 H), 4.30 (d, J = 12.0 Hz, 1 H),
4.34 (d, J = 12.0 Hz, 1 H), 6.70–6.82 (m, 2 H), 6.96–7.03
(m, 4 H), 7.17–7.37 (m, 7 H). 13C NMR (100 MHz, CDCl3):
d = 30.1, 30.2, 46.4, 126.4, 126.8, 127.3, 127.4, 128.0, 128.4,
128.8, 129.2, 129.4, 130.4, 131.9, 134.1, 135.3, 142.2,
143.1, 161.5, 188.5. HRMS (ESI+): m/z [M + H]+ calcd for
C23H20N3O2S3: 466.0712; found: 466.0700. The purity of the
product was confirmed by HPLC using the same two
conditions used for 6b. The retention time of the product
under conditions A was 12.7 min (96% purity) and under
conditions B was 15.1 min (98% purity).
(11) Compound 5d: 1H NMR (400 MHz, CDCl3): d = 2.76–2.92
(m, 2 H), 3.34–3.49 (m, 2 H), 6.05 (br s, 2 H), 7.18–7.52 (m,
8 H). 13C NMR (100 MHz, CDCl3): d = 30.0, 30.5, 126.7,
127.8, 128.3, 129.1, 129.3, 130.0, 131.7, 135.7, 136.9,
140.1, 143.7, 183.3. HRMS (ESI+): m/z [M + H]+ calcd for
C15H15N2S: 255.0951; found: 255.0951. HPLC conditions
A: MeCN/H2O with 0.1% AcOH and conditions B: MeOH/
H2O with 0.1% AcOH. The following gradient was used:
35% organic solvent for 3 min, 35–95% organic solvent over
15 min, 95% organic solvent for 2 min at 1.0 mL/min. The
retention time of the product under conditions A was 6.6 min
(>99% purity) and under conditions B was 10.5 min (>99%
purity).
(8) Compound 1: 1H NMR (400 MHz, CDCl3): d = 4.38 (s,
2 H), 6.90–7.44 (m, 15 H). 13C NMR (100 MHz, CDCl3):
d = 46.46, 126.7, 126.8, 127.7, 127.9, 128.8, 128.9, 129.3,
129.4, 129.5, 131.9, 144.0, 144.8, 161.8, 188.4. HRMS
(ESI+): m/z [M + H]+ calcd for C21H18N3O2S3: 440.0556;
found: 440.0545. HPLC conditions A: MeCN/H2O with
0.1% AcOH and the following gradient: 5% MeCN for
2 min, 5–95% MeCN over 16 min, 95% MeCN for 2 min at
0.5 mL/min. HPLC conditions B: MeOH/H2O with 0.1%
AcOH and the following gradient: 5% MeOH for 2 min, 5–
95% MeOH over 16 min, 95% MeOH for 2 min at 1.0 mL/
min. The retention time of the product under conditions A
was 16.9 min (>99% purity) and under conditions B it was
17.9 min (>99% purity).
Crystal Data: CCDC 838607.22 C15H14N3S; MW = 254.34;
monoclinic; a = 7.3785 (10) Å, b = 15.847 (3) Å, c =
11.1495 (16) Å, b = 101.204 (14)°; U = 1278.8 (3) Å3;
T = 298 (2) K; space group P 21/n (#14); l = 0.71073 Å;
Z = 4; Dc = 1.321 Mg/m3; F(000) = 536; colorless;
dimensions 0.20 × 0.20 × 0.50 mm; m = 0.235 mm–1; 3.32 <
Q < 32.23°, 7898 reflection measured, 4179 unique
reflections, Rint = 0.0773. R1 = 0.2121, 0.3045,
Compound 6a: 1H NMR (400 MHz, CDCl3): d = 1.83 (d,
J = 6.8 Hz, 3 H), 4.51 (q, J = 6.8 Hz, 1 H), 6.85–7.50 (m,
15 H). 13C NMR (100 MHz, CDCl3): d = 14.7, 55.1, 126.7,
126.8, 127.6, 127.9, 128.6, 128.6, 129.2, 129.4, 129.4,
132.2, 144.1, 144.8, 160.7, 188.4. HRMS (ESI+): m/z [M +
H]+ calcd for C22H20N3O2S3: 454.0712; found: 454.0701.
HPLC conditions A: MeCN/H2O with 0.1% AcOH and the
following gradient: 45% MeCN for 3 min, 45–95% MeCN
over 15 min, 95% MeCN for 2 min at 1.0 mL/min. HPLC
conditions B: MeOH/H2O with 0.1% AcOH and the
following gradient: 55% MeOH for 3 min, 55–95% MeOH
over 15 min, 95% MeOH for 2 min at 1.0 mL/min. The
retention time of the product under conditions A was 17.4
min (>99% purity) and under conditions B was 18.0 min
(>99% purity).
wR2 = 0.2746, 0.3530, 1.772 goodness of fit on F2. Crystals
are invariably twinned. The structure was solved by direct
methods with SHELXS-86 and refined by full-matrix least-
squares with SHELXL-97. In each case, non-hydrogen
atoms were found in the initial E-maps. All non-hydrogen
atom positions and anisotropic vibrational parameters
were refined in the developed models, which included
contributions from the hydrogen atoms placed in calculated
positions and assigned Uiso values equal to 120% of the Ueq
of the adjacent atom.
Compound 6b: 1H NMR (400 MHz, CDCl3): d = 1.91 (s,
6 H), 6.90–7.02 (m, 4 H), 7.02–7.14 (m, 3 H), 7.14–7.22 (m,
2 H), 7.22–7.42 (m, 6 H). 13C NMR (100 MHz, CDCl3): d =
23.4, 63.7, 126.7, 126.8, 127.6, 127.9, 128.4, 128.7, 129.2,
129.3, 129.3, 132.5, 144.1, 144.9, 160.1, 188.5. HRMS
(ESI+): m/z [M + H]+ calcd for C23H22N3O2S3: 468.0869;
found: 468.0860. HPLC conditions A: MeCN/H2O with
0.1% AcOH and conditions B: MeOH/H2O with 0.1%
AcOH. The following gradient was used: 40% organic
(12) Georgiev, A. G.; Daskalov, H. P. 5-Substituted derivatives of
5H-dibenz(b,f)azepine and method for obtaining the same;
US 4,124,583, 1978.
(13) (a) Sheldrick, G. M. Acta Crystallogr., Sect. A; 2008, 64,
112. (b) Sheldrick, G. M. Program for crystal structure
solution and refinement; University of Göttingen: Germany,
1998.
Synlett 2012, 23, 301–305
© Thieme Stuttgart · New York