V. V. Shmanai, V. A. Korshun et al.
FULL PAPER
5-H, 5Ј-H), 8.08 (d, J = 8.3 Hz, 2 H, 6-H, 6Ј-H), 7.79 (m, 2 H, 4- (MALDI+): calcd. for C43H49N2O2 [M – Cl]+ 625.3789; found
+
H, 4Ј-H), 7.68 (m, 2 H, 8-H, 8Ј-H), 7.54 (m, 2 H, 7-H, 7Ј-H), 6.66
(d, Ja,b = Jb,c = 13.5 Hz, 2 H, a-H, c-H), 4.29 (m, 4 H, NCH2),
2.24 (t, J = 7.2 Hz, 2 H, COCH2), 2.01 (s, 12 H, 1-CH3, 1Ј-CH3),
1.81 (m, 4 H, NCH2CH2), 1.60 (m, 2 H, COCH2CH2), 1.50 (m, 4
H, NCH2 CH2 CH2 , CH2 CH3 ), 0.96 (t, J = 7.3 Hz, 3 H,
CH2CH3) ppm. 13C NMR ([D6]DMSO): δ = 175.17, 175.13 (C-2,
C-2Ј), 174.35 (CO), 148.56 (C-b), 139.62 (2 C, C-3a, C-3aЈ), 133.21,
133.17 (C-9b, C-9bЈ), 131.54 (2 C, C-5a, C-5aЈ), 130.51 (2 C, C-5,
C-5Ј), 129.98 (2 C, C-6, C-6Ј), 127.93 (2 C, C-8, C-8Ј), 127.46 (2
C, C-9a, C-9aЈ), 125.09 (2 C, C-7, C-7Ј), 122.22 (2 C, C-9, C-9Ј),
111.82 (2 C, C-4, C-4Ј), 102.19, 102.16 (C-a, C-c), 50.63 (2 C, C-1,
C-1Ј), 43.94 (2 C, NCH2), 33.56 (COCH2), 29.59 (CH2CH2CH3),
28.38 (COCH2CH2CH2CH2), 27.18 (2 C), 27.17 (2 C) (1-CH3, 1Ј-
CH3), 25.71 (COCH2CH2CH2), 24.34 (COCH2CH2), 19.59
(CH2CH3), 13.90 (CH2CH3) ppm. HRMS (MALDI+): calcd. for
625.3812.
General Procedure for the Preparation of Cyanine Amido Alcohols
5a–d: The corresponding cyanine acid 4a–d (15.0 mmol) and DIEA
(4.96 mL, 30.0 mmol) were dissolved in DMF (60 mL). PyBOP
(7.81 g, 15.0 mmol) was added in one portion and the reaction mix-
ture was stirred for 5 min at ambient temperature. A solution of
trans-4-aminocyclohexanol hydrochloride (2.28 g, 15.0 mmol) in
DMF (30 mL) was added; the mixture was stirred for 4 h and then
diluted with chloroform (500 mL), washed with water (2ϫ200 mL)
and brine (200 mL), dried with Na2SO4, and the solvents evapo-
rated. The residue was purified by chromatography on silica gel
using ethanol in chloroform as eluent (gradient of 0Ǟ5%) to give
the desired amide.
2-[3-(1,3,3-Trimethyl-2,3-dihydroindol-2-ylidene)-1-propenyl]-3,3-di-
methyl-1-[5-(trans-4-hydroxycyclohexylaminocarbonyl)pentyl]-3H-in-
dolium Hexafluorophosphate (5a): Compound 5a was prepared
from 4a. Yield 8.10 g (77%), dark-purple foam. TLC: Rf = 0.42
C41H47N2O2 [M – Cl]+ 599.3632; found 599.3635.
+
2-[5-(1,3,3-Trimethyl-2,3-dihydro-1H-indol-2-ylidene)-1,3-pentadi-
enyl]-3,3-dimethyl-1-(5-carboxypentyl)-3H-indolium Chloride (4c):
Compound 4c was prepared from 3a, malondialdehyde bis(phenyl-
imine) monohydrochloride, and 2a. Yield 17.4 g (67%), dark-blue
foam. TLC: Rf = 0.26 [10% MeOH in CHCl3 (v/v)]. 1H NMR ([D6]-
1
[15% MeOH in CHCl3 (v/v)]. H NMR ([D6]DMSO): δ = 8.35 (t,
Ja,b = Jb,c = 13.4 Hz, 1 H, b-H), 7.63 (m, 2 H, 4-H, 4Ј-H), 7.57 (d,
J = 8.0 Hz, 1 H, NH), 7.45 (m, 4 H, 6-H, 7-H, 6Ј-H, 7Ј-H), 7.30
(m, 2 H, 5-H, 5Ј-H), 6.47 (d, Ja,b = Jb,c = 13.4 Hz, 2 H, a-H, c-H),
4.49 (d, J = 4.3 Hz, 1 H, OH), 4.10 (t, J = 7.5 Hz, 2 H, NCH2),
3.66 (s, 3 H, NCH3), 3.40 (m, 1 H, 4ЈЈ-H), ca. 3.30 (m, 1 H, 1ЈЈ-
H), 2.03 (t, J = 7.0 Hz, 2 H, COCH2), 1.80–1.60 (m, 18 H, 3-CH3,
3Ј-CH3, 2’’eq-H, 3ЈЈeq-H, 5ЈЈeq-H, 6ЈЈeq-H, NCH2CH2), 1.54 (m, 2
H, COCH2CH2), 1.37 (m, 2 H, NCH2CH2CH2), 1.10 (m, 4 H,
2ЈЈax-H, 3ЈЈax-H, 5ЈЈax-H, 6ЈЈax-H) ppm. 13C NMR ([D6]DMSO): δ
= 174.54, 173.76 (C-2, C-2Ј), 171.07 (CO), 149.75 (C-b), 142.71 (C-
7aЈ), 141.99 (C-7a), 140.64 (2 C, C-3a, C-3aЈ), 128.70, 128.66 (C-
6, C-6Ј), 125.33, 125.20 (C-5, C-5Ј), 122.55, 122.47 (C-4, C-4Ј),
111.58 (2 C, C-7, C-7Ј), 103.00, 102.45 (C-a, C-c), 68.22 (C-1ЈЈ),
48.93 (2 C, C-3, C-3Ј), 47.04 (C-4ЈЈ), 43.78 (NCH2), 35.21
(COCH2), 34.04 (2 C, C-2ЈЈ, C-6ЈЈ), 31.43 (NCH3), 30.40 (2 C) (C-
3ЈЈ, C-5ЈЈ), 27.52 (2 C), 27.33 (2 C) (3-CH3, 3Ј-CH3), 26.84
(NCH2CH2), 25.74 (NCH2CH2CH2), 25.00 (COCH2CH2) ppm.
DMSO): δ = 12.07 (br. s, 1 H, CO2H), 8.32 (t, Ja,b = Jb,c = Jc,d
=
Jd,e = 13.0 Hz, 2 H, b-H, d-H), 7.60 (m, 2 H, 4-H, 4Ј-H), 7.39 (m,
4 H, 6-H, 7-H, 6Ј-H, 7Ј-H), 7.25 (m, 2 H, 5-H, 5Ј-H), 6.58 (t, Jb,c
= Jc,d = 13.0 Hz, 1 H, c-H), 6.31 (d, Ja,b = 13.0 Hz, 1 H, a-H), 6.26
(d, Jd,e = 13.0 Hz, 1 H, e-H), 4.09 (m, 2 H, NCH2), 3.60 (s, 3 H,
NCH3), 2.20 (t, J = 7.2 Hz, 2 H, COCH2), 1.70 (m, 2 H,
NCH2CH2), 1.68 (s, 12 H, 3-CH3, 3Ј-CH3), 1.55 (m, 2 H,
COCH2CH2), 1.39 (m, 2 H, NCH2CH2CH2) ppm. 13C NMR ([D6]-
DMSO): δ = 174.30 (CO), 173.31 (C-2Ј), 172.56 (C-2), 154.03 (2
C, C-b, C-d), 142.80 (C-7aЈ), 142.06 (C-7a), 141.13 (C-3a), 141.06
(C-3aЈ), 128.45 ppm. 128.38 (C-6, C-6Ј), 125.41 (C-c), 124.77,
124.65 (C-5, C-5Ј), 122.46, 122.34 (C-4, C-4Ј), 111.08 (2 C, C-7, C-
7Ј), 103.35 (C-e), 103.09 (C-a), 48.91 (2 C, C-3, C-3Ј), 43.28
(NCH2), 33.52 (COCH2), 31.18 (NCH3), 27.22 (2 C), 27.05 (2 C)
(3-CH3, 3Ј-CH3), 26.71 (NCH2CH2), 25.68 (NCH2CH2CH2), 24.22
31P NMR ([D6]DMSO): δ = –144.18 (sept, JP, F = 711 Hz,
1
+
(COCH2CH2) ppm. HRMS (MALDI+): calcd. for C32H39N2O2
PF6–) ppm. HRMS (MALDI+): calcd. for C36H48N3O2 [M –
+
[M – Cl]+ 483.3006; found 483.3018.
PF6]+ 554.3741; found 554.3760.
2-[5-(3-Butyl-1,1-dimethyl-1,2-dihydro-3H-benzo[e]indol-2-ylidene)-
1,3-pentadienyl]-1,1-dimethyl-3-(5-carboxypentyl)-1H-benzo[e]indol-
ium Chloride (4d): Compound 4d was prepared from 3b, malondial-
dehyde bis(phenylimine) monohydrochloride, and 2b. Yield 16.7 g
(51%), dark-green foam. TLC: Rf = 0.25 [10% EtOH in DCM
2-[3-(3-Butyl-1,1-dimethyl-1,2-dihydrobenzo[e]indol-2-ylidene)-1-pro-
penyl]-1,1-dimethyl-3-[5-(trans-4-hydroxycyclohexylaminocarbonyl)-
pentyl]-1H-benzo[e]indolium Hexafluorophosphate (5b): Compound
5b was prepared from 4b. Yield 10.16 g (80%), dark-violet foam.
TLC: Rf = 0.40 [15% MeOH in CHCl3 (v/v)]. 1H NMR ([D6]-
DMSO): δ = 8.59 (t, Ja,b = Jb,c = 13.4 Hz, 1 H, b-H), 8.30 (m, 2
H, 9-H, 9Ј-H), 8.11 (m, 4 H, 5-H, 5Ј-H, 6-H, 6Ј-H), 7.79 (m, 2 H,
1
(v/v)]. H NMR ([D6]DMSO): δ = 12.17 (br. s, 1 H, CO2H), 8.46
(t, Jb,c = Jc,d = 13.4 Hz, 2 H, b-H, d-H), 8.26 (d, J = 8.2 Hz, 2 H,
9-H, 9Ј-H), 8.07 (m, 4 H, 5-H, 5Ј-H, 6-H, 6Ј-H), 7.74 (m, 2 H, 4- 4-H, 4Ј-H), 7.69 (m, 2 H, 8-H, 8Ј-H), 7.55 (m, 3 H, 7-H, 7Ј-H,
H, 4Ј-H), 7.68 (m, 2 H, 8-H, 8Ј-H), 7.51 (m, 2 H, 7-H, 7Ј-H), 6.66
(t, Jb,c = Jc,d = 13.0 Hz, 1 H, c-H), 6.37 (d, Ja,b = Jd,e = 13.4 Hz,
NH), 6.58 (m, 2 H, a-H, c-H), 4.44 (d, J = 4.6 Hz, 1 H, OH), 4.27
(m, 4 H, NCH2), 3.39 (m, 1 H, 4ЈЈ-H), 3.24 (m, 1 H, 1ЈЈ-H), 2.02
2 H, a-H, e-H), 4.24 (m, 4 H, NCH2), 2.21 (m, 2 H, COCH2), 1.97 (m, 14 H, COCH2, 1-CH3, 1Ј-CH3), 1.80 (m, 4 H, NCH2CH2),
(s, 12 H, 1-CH3, 1Ј-CH3), 1.74 (m, 4 H, NCH2CH2), 1.57 (m, 2 H, 1.71–1.37 (m, 10 H, COCH2CH2CH2, 2ЈЈeq-H, 3ЈЈeq-H, 5ЈЈeq-H,
COCH2CH2), 1.44 (m, 4 H, NCH2CH2CH2, CH2CH3), 0.95 (t, J 6ЈЈeq-H, CH2CH3), 1.05 (m, 4 H, 2ЈЈax-H, 3ЈЈax-H, 5ЈЈax-H, 6ЈЈax-H),
= 7.3 Hz, 3 H, CH2CH3) ppm. 13C NMR ([D6]DMSO): δ = 174.31,
173.70, 171.31 (CO, C-2, C-2Ј), 152.87 (2 C, C-b, C-d), 139.76 (2
0.97 (t, J = 7.3 Hz, 3 H, CH2CH3) ppm. 13C NMR ([D6]DMSO): δ
= 175.18 (2 C, C-2, C-2Ј), 171.03 (CO), 148.54 (C-b), 139.68, 139.64
C, C-3a, C-3aЈ), 133.20 (2 C, C-9b, C-9bЈ), 131.33 (2 C, C-5a, C- (C-3a, C-3aЈ), 133.22, 133.15 (C-9b, C-9bЈ), 131.57 (2 C, C-5a, C-
5aЈ), 130.34 (2 C, C-5, C-5Ј), 129.95 (2 C, C-6, C-6Ј), 127.77 (2 C,
C-8, C-8Ј), 127.64 (2 C, C-9a, C-9aЈ), 126.16 (C-c), 124.82 (2 C, C-
7, C-7Ј), 122.09 (2 C, C-9, C-9Ј), 111.65 (2 C, C-4, C-4Ј), 103.01 (2
5aЈ), 130.55, 130.51 (C-5, C-5Ј), 129.99 (2 C, C-6, C-6Ј), 127.96 (2
C, C-8, C-8Ј), 127.48 (2 C, C-9a, C-9aЈ), 125.14 (2 C, C-7, C-7Ј),
122.25 (2 C, C-9, C-9Ј), 111.84 (2 C, C-4, C-4Ј), 102.11 (2 C, C-a,
C, C-a, C-e), 50.75 (2 C, C-1, C-1Ј), 43.44 (2 C, NCH2), 33.54 C-c), 68.21 (C-1ЈЈ), 50.68 (2 C, C-1, C-1Ј), 47.02 (C-4ЈЈ), 43.92 (2
(COCH2), 29.43 (CH2CH2CH3), 27.01 (COCH2CH2CH2CH2), C, NCH2), 35.20 (COCH2), 34.00 (2 C, C-2ЈЈ, C-6ЈЈ), 30.38 (2 C,
26.86 (4 C, 1-CH3, 1Ј-CH3), 25.68 (COCH2CH2CH2), 24.27 C-3ЈЈ, C-5ЈЈ), 29.59 (CH2CH2CH3), 27.19 (2 C), 27.13 (2 C) (1-
(COCH2CH2), 19.51 (CH2CH3), 13.82 (CH2CH3) ppm. HRMS CH3, 1Ј-CH3), 25.67 (COCH2CH2CH2), 25.02 (COCH2CH2), 19.63
2112
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Eur. J. Org. Chem. 2008, 2107–2117