10.1002/cmdc.202100204
ChemMedChem
FULL PAPER
concentrated under reduced pressure to obtain target compound 23 (2.76
g, 11.40 mmol) as yellow oil and in a yield of 93%. 1H NMR (500 MHz,
CDCl3) δ 9.88 (s, 1H), 8.63 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 1.9 Hz, 1H),
7.82 (dd, J = 1.8, 8.5 Hz, 1H), 2.77 (s, 1H), 2.30 (s, 3H). Data consistent
with literature.
eluent. The solvent was then removed under reduced pressure and the
mixture was extracted with DCM (3 50 mL) from water. The organic
phases were combined and dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The crude was purified using
column chromatography packed with silica gel using hexane:ethyl
acetate= 99.5:0.5. Target compound 26 (234 mg, 0.633 mmol) was
obtained as a yellow solid in a yield of 43%. 1H NMR (500 MHz, CDCl3) δ
7.83 (d, J = 2.2 Hz, 1H), 7.55 – 7.67 (m, 6H), 7.49 (dd, J = 2.3, 8.5 Hz, 1H),
7.44 (t, J = 7.6 Hz, 2H), 7.31 – 7.38 (m, 1H), 7.21 (d, J = 8.6 Hz, 1H), 5.27
(s, 2H), 3.54 (s, 3H). 13C NMR (126 MHz, CDCl3, 27°C) δ 153.25, 140.59,
140.24, 138.29, 135.99, 131.82, 128.88, 127.61, 127.46, 127.18, 127.07,
126.98, 116.35, 113.36, 95.19, 56.47.
N-(2-bromo-4-vinylphenyl)acetamide 24 [NEW]
A suspension of NaH 60% (3 equiv., 2.50 g, 30.98 mmol) in anhydrous
DCM (20 mL) was slowly added compound 11 (1.2 equiv., 5.01 g, 12.39
mmol) at 0 oC, which was stirred for 30 min. Then, compound 23 (2.50 g,
10.33 mmol) was added to the mixture, that was stirred at 20 oC for 16 h.
The reaction mixture was then quenched using sat. NaHCO3 in water. The
crude mixture was extracted with DCM (3 250 mL), dried over anhydrous
Na2SO4, filter, and purified using column chromatography packed with
silica gel with hexane:ethyl acetate= 9:1 as eluent to obtain the desired
compound 24 (2.01 g, 8.37 mmol) as transparent oil in a yield of 81%. 1H
NMR (500 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 1.8 Hz, 1H),
7.35 (dd, J = 1.9, 8.5 Hz, 1H), 6.60 (dd, J = 10.9, 17.6 Hz, 1H), 5.69 (d, J
= 17.5 Hz, 1H), 5.25 (d, J = 10.9 Hz, 1H), 2.24 (s, 3H).
(E)-3-(3-bromo-4-(methoxymethoxy)styryl)-1,1'-biphenyl 27 [NEW]
Compound 12 (500 mg, 2.06 mmol), 2,3-di(pyridin-2-yl)pyrazine (5%, 24
mg, 102 µmol), Pd(OAc)2 (5%, 23 mg, 102 µmol), [1,1'-biphenyl-3-
ylboronic acid (1.1 equiv., 448 mg, 2.26 mmol), and Cu(OAc)2
monohydrate (1.5 equiv., 615 mg, 3.09 mmol) were transferred to a
reaction flask (25 mL) and dissolved in DMF (8 mL). The reaction mixture
was stirred at 20 oC for 18 h. The progress of the reaction was monitored
by TLC with hexane:ethyl acetate=9:1 as eluent. The mixture was
extracted with DCM (3 50 mL) from a solution EDTA in water (0.2 M).
The organic phases were combined, dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure. The mixture was purified using
column chromatography packed with silica gel with hexane:ethyl
acetate=99.5:0.5 as eluent to obtain title compound 27 (698 mg, 1.77
mmol) as a white solid in a yield of 86%. 1H NMR (500 MHz, CDCl3) δ 7.77
(d, J = 2.2 Hz, 1H), 7.71 (t, J = 1.6 Hz, 1H), 7.61 – 7.67 (m, 2H), 7.37 –
7.51 (m, 7H), 7.16 (d, J = 8.5 Hz, 1H), 7.07 (s, 2H), 5.28 (s, 2H), 3.55 (s,
3H).13C NMR (126 MHz, CDCl3, 27°C) δ 153.27, 141.79, 141.09, 137.59,
132.83, 131.11, 129.16, 128.82, 128.38, 127.46, 127.22, 127.07, 126.79,
126.61, 125.39, 125.34, 116.14, 113.29, 95.15, 56.44.
(E)-N-(2-bromo-4-styrylphenyl)acetamide 25 [NEW]
Compound 24 (500 mg, 2.08 mmol), 2,3-di(pyridin-2-yl)pyrazine (5%, 24
mg, 104 µmol), Pd(OAc)2 (5%, 23 mg, 104 µmol), phenylboronic acid (1.1
equiv., 279 mg, 2.29 mmol), Cu(OAc)2 monohydrate (1.5 equiv., 623 mg,
3.12 mmol) were dissolved in DMF (8 mL). The reaction mixture was
stirred at 20 oC for 18 h. The reaction progress was monitored by TLC
using hexane:ethyl acetate= 9:1 as eluent. The mixture was extracted with
DCM (3 50 mL) from a solution EDTA in water (0.2 M). The organic
phases were combined, dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The mixture was purified column
chromatography packed with silica gel using hexane:ethyl acetate=95:5 to
obtain target product 25 (241 mg, 0,762 mmol) as a white solid in a yield
of 36%. 1H NMR (500 MHz, CDCl3) δ 8.27 (d, J = 8.5 Hz, 1H), 7.59 – 7.63
(m, 1H), 7.55 (s, 1H), 7.41 (d, J = 7.4 Hz, 2H), 7.36 (dd, J = 1.8, 8.6 Hz,
1H), 7.28 (t, J = 7.6 Hz, 2H), 7.15 – 7.23 (m, 1H), 6.86 – 6.99 (m, 2H), 2.16
(s, 3H).13C NMR (126 MHz, CDCl3, 27°C) δ 168.10, 136.91, 134.83,
134.71, 131.45, 129.81, 129.26, 128.75, 127.91, 126.56, 126.52, 121.68,
113.42, 22.72
(E)-5-(2-([1,1'-biphenyl]-3-yl)vinyl)-2-hydroxybenzoic
acid
DC18
[NEW]
Oxalic acid (3 equiv., 102 mg, 1.14 mmol), Pd(OAc)2 (5%, 4 mg, 19 µmol),
Xantphos (5%, 11 mg, 19 µmol), compound 27 (150 mg, 379 µmol), H2O
(10 equiv., 68 mg, 68 µL, 3.79 mmol), and DMF (7 mL) were transferred to
a reactor tube that was sealed. The septum was penetrated with a syringe
needle that was attached to a balloon (for pressure equalization during the
in-situ CO production). The mixture was stirred and heated at 100 oC
(E)-2-acetamido-5-styrylbenzoic acid DC16 [380365-20-8]
Oxalic acid (3 equiv., 85 mg, 948 µmol), Pd(OAc)2 (5%, 4 mg, 16 µmol),
Xantphos (5%, 9 mg, 16 µmol), compound 25 (100 mg, 316 µmol), H2O
(10 equiv., 57 mg, 57 µL, 3.16 mmol) and DMF (5 mL) were transferred to
whereupon TEA (3 equiv.
2O
(3 equiv., 116 mg, 107 µL, 1.14 mol) was then added over a period of 15
min. by means of a syringe pump. During the addition, CO was formed
through the degradation of the oxalic acid. The reaction mixture was then
stirred at 100 oC for 3 h. The reaction mixture was extracted with DCM (3
50 mL) from HCl (0.1 M). The combined organic phases were dried over
anhydrous Na2SO4, filtered, and the solvent was removed under reduced
pressure. The crude was purified using a chromatography column packed
with silica gel with 1% formic acid in DCM as eluent to obtain target
compound DC18 (52 mg, 164 µmol) in a yield of 43%. 1H NMR (500 MHz,
DMSO) δ 7.96 (d, J = 2.2 Hz, 1H), 7.84 (s, 1H), 7.78 (dd, J = 2.3, 8.7 Hz,
1H), 7.66 (dd, J = 1.0, 8.1 Hz, 2H), 7.52 (d, J = 7.7 Hz, 1H), 7.48 (d, J =
7.9 Hz, 1H), 7.37 – 7.44 (m, 3H), 7.3 – 7.35 (m, 2H), 7.16 (d, J = 16.5 Hz,
1H), 6.94 (d, J = 8.6 Hz, 1H).13C NMR (126 MHz, DMSO, 27°C) δ 171.77,
160.69, 140.55, 140.06, 137.83, 133.11, 129.24, 128.88, 128.58, 128.53,
127.75, 127.52, 126.75, 126.71, 125.68, 125.38, 124.63, 117.67, 113.14.
[M-H]-: Calcd for C21H15O3 315.10212, found 315.10192.
o
a reaction tube, which was sealed and stirred and heated at 100 C. The
septum was penetrated with a syringe needle that was attached to a
balloon (for pressure equalization during the in-situ CO production). TEA
(3 equiv.
2O (3 equiv., 97
mg, 89 µL, 948 µmol) was added over a period of 15 min. by means of a
syringe pump. During the addition CO was formed through degradation of
the oxalic acid. The reaction mixture was stirred and heated at 100 oC for
3 h. Then, the reaction mixture was extracted with DCM (3 50 mL) from
HCl (0.1 M). The combined organic phases were dried over anhydrous
Na2SO4, filtered, and the solvent was removed under reduced pressure.
The crude was purified with a chromatography column packet with silica
gel using DCM:methanol=9:1 and 1% formic acid as eluent to obtain title
compound DC16 (38 mg, 135 µmol) in a yield of 42%. 1H NMR (500 MHz,
DMSO) δ 11.26 (s, 1H), 8.49 (d, J = 8.7 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H),
7.85 (dd, J = 2.0, 8.7 Hz, 1H), 7.62 (d, J = 7.4 Hz, 2H), 7.38 (t, J = 7.7 Hz,
2H), 7.19 – 7.32 (m, 4H), 2.15 (s, 3H). 13C NMR (126 MHz, DMSO) δ
169.33, 168.36, 140.04, 136.98, 131.32, 131.03, 129.26, 128.68, 128.36,
127.96, 127.59, 127.17, 126.44, 120.09, 25.01.
(E)-2-(3-bromo-4-(methoxymethoxy)styryl)-1,1'-biphenyl 28 [NEW]
Compound 12 (500 mg, 2.06 mmol), 2,3-di(pyridin-2-yl)pyrazine (5%, 24
mg, 102 µmol), Pd(OAc)2 (5%, 23 mg, 102 µmol), [1,1'-biphenyl-2-
ylboronic acid (1.1 equiv., 448 mg, 2.26 mmol), and Cu(OAc)2
monohydrate (1.5 equiv., 615 mg, 3.09 mmol) were transferred to a flask
and dissolved with DMF (8 mL) that was stirred at 20 oC for 18 h. The
progress of the reaction was monitored by TLC using hexane:ethyl
acetate=9:1 as eluent. The mixture was extracted with DCM (3 50 mL)
from a solution EDTA in water (0.2 M). The organic phases were combined
3-bromo-4-(methoxymethoxy)-1,1':4',1''-terphenyl 26 [NEW]
Compound 7b (500 mg, 1.46 mmol) in DMF (10 mL) was added [1,1’-
byphenyl]-4-ylboronic acid (1 equiv., 288 mg, 1.46 mmol), K2CO3 (2 equiv.,
402 mg, 2.92 mmol), and Pd(PPh3)4 (5%, 84 mg, 73 µmol). The reaction
mixture was flushed with argon and stirred for 2 h at 100 oC. The progress
of the reaction was monitored by TLC using hexane:ethyl acetate=9:1 as
14
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