SYNTHESIS OF A NOVEL CB CANNABINOID-PORPHYRIN CONJUGATE BASED
73
2
+
+
7
-(1,1-Dimethylheptyl)-2,4-dihydro-4,4-dime-
(94%). MS (ES ): m/z 660 [M + H] . HRMS calcd. for
thylchromeno[4,3-c]pyrazol-9-ol (4) [3]. A solution
of 3 (0.50 g, 1.44 mmol) and anhydrous hydrazine
C H N O : 659.2321. Found 659.2298.
4
4
29
5
2
5-(4-Aminophenyl)-10,15,20-triphenylporphyrin
(
0.11 mL, 3.61 mmol) in EtOH (9 mL) was stirred
(8) [26]. 5-(4-Nitrophenyl)-10,15,20-triphenylporphyrin
(7) (101 mg, 0.15 mmol) was dissolved in concentrated
hydrochloric acid (10 mL) and, while stirring, tin(II)
chloride (162 mg, 0.85 mmol) was carefully added.
The mixture was heated to 65°C for 1 h under nitrogen
atmosphere. The crude was then poured into cold water
and neutralized with ammonium hydroxide until pH 8.
The aqueous solution was extracted with CH Cl until
during 4 h at 40°C. The solvent was evaporated under
reduced pressure and the crude was purified by column
chromatography on silica gel (hexane/EtOAc, 2:1) to
furnish 4 as a yellow oil. Yield 0.40 g (81%). H NMR
(
6
1
(
1
300 MHz; CDCl ; Me Si): d , ppm 7.32–7.29 (br s, 1H),
3
4
H
.58 (d, J = 1.5 Hz, 1H), 6.51 (d, J = 1.5 Hz), 6.48 (s,
H), 1.63 (s, 6H), 1.58–1.52 (m, 2H), 1.25 (s, 6H), 1.18
2
2
1
3
s, 6H), 1.12–1.05 (m, 2H), 0.83 (t, J = 6.7 Hz, 3H). C
colorless. The organic layers were combined, dried over
Na SO , and the solvent was removed under reduced
NMR (75 MHz; CDCl ): d , ppm 153.7, 153.5, 153.4,
3
C
2
4
1
3
8
44.1, 129.1, 123.4, 106.8, 106.5, 101.7, 77.0, 44.9, 38.4,
pressure. Flash column chromatography (CH Cl )
2 2
2.2, 30.4, 30.0, 29.3, 25.0, 23.1, 14.5. HPLC-MS: [A,
afforded the title compound as a purple solid (92 mg,
+
1
0→95%], t : 3.80 min, (98%). MS (ES ): m/z 343 [M
96% yield). H NMR (300 MHz; CDCl ; Me Si): d , ppm
R
3
4
H
+
+
H] . Anal. calcd. for C H N O : C, 73.65; H, 8.83.
8.93–8.91 (m, 2H), 8.79–8.67 (m, 6H), 8.22–8.19 (m,
2
1
30
2
2
Found C, 74.01; H, 8.59.
6H), 8.10 (d, J = 7.8 Hz, 2H), 7.84–7.75 (m, 9H), 7.02 (d,
7
-(1,1-Dimethylheptyl)-1,4-dihydro-4,4-dimethyl-
J = 7.8 Hz, 2H), 4.02 (s, 2H), -2.69 (s, 2H). HPLC-MS:
+
chromeno[4,3-c]pyrazol-6,9-dione (5)[3]. To a solution
of 7-(1,1-dimethylheptyl)-1,4-dihydro-4,4-dimethyl-
chromeno[4,3-c]pyrazol-9-ol (4) (130 mg, 0.38 mmol)
[iso 95%–5%], t : 6.13 min (99%). MS (ES ): m/z 630
R
+
[M + H] . HRMS calcd. for C H N : 629.2579. Found
4
4
31
5
629.2583.
in MeCN/H O (6:1, 2.5 mL) a solution of BTIB
2-{2-Oxo-2-[(4-(10,15,20-triphenylporphyrin-5-
yl)phenyl)amino]ethoxy}acetic acid (9) [27]. To a
solution of aminoporphyrin 8 (340 mg, 0.53 mmol) in
DMF (3 mL) diglycolic anhydride (93 mg, 0.80 mmol)
was added. The reaction was stirred at room temperature
2
(
490 mg, 1.14 mmol) in MeCN/H O (6:1, 2 mL) was
2
added dropwise. The reaction mixture was stirred at
room temperature for 15 min, neutralized with aqueous
NaHCO saturated solution, and extracted with diethyl
3
ether. The organic layer was washed with H O, dried
overnight. The crude was diluted with CHCl and hexane
2
3
over MgSO and concentrated. Column chromatography
on silica gel (hexane/EtOAc, 1:2) afforded the title
until precipitation occurred. The precipitate was filtered
and washed with water to remove residual anhydride and
then dried under vacuum to obtain the title compound
4
compound as a red solid. Yield 29 mg (21%). mp
1
1
8
8
5–86°C. H NMR (300 MHz; CDCl ; Me Si): d , ppm
as a purple solid. Yield 340.9 mg (85%). H NMR (300
3
4
H
.41 (br s, 1H), 7.40 (s, 1H), 6.69 (s, 1H), 1.59–1.57
MHz; CDCl ; Me Si): d , ppm 9.01–8.94 (m, 2H), 8.82–
3
4
H
(
(
br s, 6H), 1.55–1.48 (m, 2H), 1.30 (s, 6H), 1.27–1.23
8.79 (m, 6H), 8.31–8.16 (m, 10H), 7.78–7.64 (m, 9H),
4.61 (s, 2H), 4.45 (s, 2H), -2.75 (br s, 2H). HRMS calcd.
for C H N O : 745.2689. Found 745.2701.
1
3
m, 6H), 1.19–1.12 (br s, 2H), 0.86–0.82 (m, 3H).
C
NMR (75 MHz; CDCl ): d , ppm 184.1, 180.9, 160.2,
3
C
48 35
5
4
1
2
7
61.2, 137.8, 132.0, 130.4, 129.5, 113.8, 78.6, 43.3, 30.9,
5-[4-(3,5-Dioxomorpholino)phenyl]-10,15,20-
triphenylporphyrin (10). A solution of compound 9
9.6, 28.7, 27.4, 25.1, 23.2, 21.8, 14.0. HPLC-MS: [A,
+
0%→100%], t : 3.37 min (98%). MS (ES ): m/z 357
(40 mg, 0.05 mmol) in toluene (2 mL) and SOCl (6 mL,
R
2
+
[
M + H] . Anal. calcd. for C H N O : C, 70.76; H, 7.92.
0.08 mmol) was heated at 120°C under microwave
irradiationconditionsfor30min.Thesolventwasremoved
under vacuum and the corresponding acyl chloride
was used for the next step without further purification.
A solution of 5 (14 mg, 0.04 mmol) in anhydrous CH Cl
2
1
28
2
3
Found C, 71.03; H, 8.24.
5
-(4-Nitrophenyl)-10,15,20-triphenylporphyrin
(
(
7) [26]. To a solution of meso-tetraphenylporphyrin
TPP, 6) (500 mg, 0.81 mmol) in TFA (25 mL) sodium
2
2
nitrite (99 mg, 1.40 mmol) was added and the reaction
mixture was stirred for 3 min at room temperature. After
that, the crude was poured into water and extracted
three times with CH Cl . The organic layers combined
(1 mL) was added to a precooled suspension of NaH
(3 mg, 0.12 mmol) in CH Cl , the mixture was stirred for
2
2
10 min under nitrogen atmosphere. After that, the acyl
chloride (30 mg, 0.04 mmol), dissolved in anhydrous
CH Cl (1 mL), was rapidly added and the reaction was
2
2
and washed with saturated aqueous NaHCO and water.
3
2
2
The mixture was dried over anhydrous Na SO and the
stirred for 30 min. The reaction mixture was then diluted
with CH Cl and washed with water and brine. The
2
4
solvent was removed under vacuum. Flash column
chromatography (CH Cl ) provided the title compound
2
2
organic layer was dried over Na SO and concentrated
2
2
2
4
1
as a purple solid. Yield 262 mg (49%). H NMR
under reduced pressure. Column chromatography
on silica gel (MeOH/CH Cl , 1:12) afforded the title
(
8
300 MHz; CDCl ; Me Si): d , ppm 9.03–8.99 (m, 2H),
3
4
H
2
2
.86–8.79 (m, 6H), 8.59 (d, J = 8.1 Hz, 2H), 8.28 (d,
undesired compound as a purple solid.Yield 15 mg (52%).
1
J = 8.1 Hz, 2H), 8.19–8.12 (m, 6H), 7.81–7.64 (m, 9H),
2.77 (s, 2H). HPLC-MS: [iso 95%–5%], t : 10.0 min
H NMR (300 MHz; CDCl3; Me Si): d , ppm 8.99–8.87
4
H
-
(m, 2H), 8.80–8.72 (m, 6H), 8.23–8.15 (m, 8H), 7.97 (d,
R
Copyright © 2017 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2017; 21: 73–76