A R T I C L E S
Gabe et al.
2.5 mmol) and 2,4-dimethyl-3-ethylpyrrole (616 mg, 5.0 mmol) were
dissolved in 100 mL of absolute CH2Cl2 under an Ar atmosphere. One
drop of TFA was added, and the solution was stirred at room
temperature overnight. A solution of DDQ (585 mg, 2.5 mmol) in CH2-
Cl2 was added, and stirring was continued for 15 min. The reaction
mixture was washed with water, dried over MgSO4, filtered, and
evaporated. The crude compound was purified by column chromatog-
raphy over aluminum oxide (CH2Cl2) to afford a brown powder (136
(EI+): calcd for M+, 421.2249; found, 421.2258. Mp: 206-207 °C.
Anal. Calcd for C23H26BF2N5: C, 65.57; H, 6.22; N, 16.62. Found: C,
65.87; H, 6.41; N, 16.36.
DAMBO-CO2Et-T. Recrystallized from CHCl3/n-hexane to afford
bright yellow needles. 1H NMR (CDCl3): δ 1.32 (t, 6H, J ) 7.1 Hz);
1.55 (s, 6H); 2.86 (s, 6H); 4.28 (q, 4H, J ) 7.1 Hz); 7.38 (dd, 1H, J
) 1.1, 8.6 Hz); 7.88 (br, 1H); 8.10 (br, 1H). HRMS (EI+): calcd for
M+, 509.2046; found, 509.2019. Mp: 229-230 °C. Anal. Calcd for
C25H26BF2N5O4‚H2O: C, 56.94; H, 5.35; N, 13.28. Found: C, 57.04;
H, 5.19; N, 12.98.
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mg, yield 14%). H NMR (CDCl3): δ 0.98 (t, 6H, J ) 7.5 Hz); 1.35
(s, 6H); 2.29 (q, 4H, J ) 7.5 Hz); 2.31 (s, 6H); 6.17 (s, 2H); 6.89 (d,
1H, J ) 8.6 Hz); 7.30 (dd, 1H, J ) 2.0, 8.6 Hz); 8.09 (d, 1H, J ) 2.0
Hz). HRMS (EI+): calcd for M+, 392.2212; found, 392.2200.
8b was similarly prepared from ethyl 2,4-dimethylpyrrole-3-car-
boxylate in 23% yield. 1H NMR (CDCl3): δ 1.33 (t, 6H, J ) 7.1 Hz);
1.77 (s, 6H); 2.58 (s, 6H); 4.26 (q, 4H, J ) 7.1 Hz); 6.28 (s, 2H); 6.95
(d, 1H, J ) 8.6 Hz); 7.27 (d, 1H, J ) 8.6 Hz); 8.08 (s, 1H). HRMS
(EI+): calcd for M+, 480.2009; found, 480.1983.
Synthesis of 3-(2-Methoxycarbonylethyl)-2,4-dimethylpyrrole
(10). Methyl 5-(benzyloxycarbonyl)-2,4-dimethyl-3-pyrrolepropionate
(3.1 g, 9.8 mmol) was dissolved in 100 mL of acetone. After the
addition of 10% Pd-C (50 mg), the mixture was stirred vigorously
under a H2 atmosphere overnight. The Pd-C was filtered off and
washed with acetone. The residue after evaporation of the filtrate was
dissolved in 10 mL of TFA and stirred at 40 °C for 10 min under an
Ar atmosphere. CHCl3 was added to the reaction mixture, and this was
washed with water. The aqueous solution was back-extracted with
CHCl3, and the combined organic extracts were washed with aqueous
sodium carbonate and water, dried over MgSO4, filtered, and evapo-
rated. The crude compound was purified by column chromatography
Synthesis of 6-(3,4-Diaminophenyl)-4,4′-diethyl-3,3′,5,5′-tetra-
methylpyrromethene (9a) and 6-(3,4-Diaminophenyl)-4,4′-diethoxy-
carbonyl-3,3′,5,5′-tetramethylpyrromethene (9b). 9a and 9b were
prepared from 8a and 8b by the same method as that used to obtain 4,
in 93% and 98% yield, respectively.
1
1
9a. H NMR (CDCl3): δ 0.98 (t, 6H, J ) 7.5 Hz); 1.35 (s, 6H);
over silica gel (CH2Cl2) to afford a yellow oil (1.6 g, yield 90%). H
2.29 (q, 4H, J ) 7.5 Hz); 2.30 (s, 6H); 3.39 (s, 2H); 3.50 (s, 2H); 6.63
(dd, 1H, J ) 1.5, 8.3 Hz); 6.64 (d, 1H, J ) 1.5 Hz); 6.74 (d, 1H, J )
8.3 Hz). HRMS (EI+): calcd for M+, 362.2470; found, 362.2472.
NMR (CDCl3): δ 2.03 (d, 3H, J ) 0.9 Hz); 2.18 (s, 3H); 2.45 (m,
2H); 2.72 (m, 2H); 3.67 (s, 3H); 6.38 (d, 1H, J ) 0.9 Hz); 7.53 (s,
1H). MS (EI): 181 (M+).
1
9b. H NMR (CDCl3): δ 1.32 (t, 6H, J ) 7.1 Hz); 1.76 (s, 6H);
Synthesis of 6-(4-Amino-3-nitrophenyl)-4,4′-bis-(2-methoxycar-
bonylethyl)-3,3′,5,5′-tetramethylpyrromethene (11). 11 was prepared
from 7 and 10 by the same method as that used to obtain 8a, in 76%
2.57 (s, 6H); 3.42 (s, 2H); 3.61 (s, 2H); 4.25 (q, 4H, J ) 7.1 Hz); 6.60
(s, 1H); 6.61 (d, 1H, J ) 8.1 Hz); 6.76 (d, 1H, J ) 8.1 Hz). HRMS
(EI+): calcd for M+, 450.2267; found, 450.2266.
1
yield. H NMR (CDCl3): δ 1.37 (s, 6H); 2.33 (s, 6H); 2.36 (t, 4H, J
) 7.1, 8.4 Hz); 2.63 (t, 4H, J ) J ) 7.1, 8.4 Hz); 3.65 (s, 6H); 6.32
(s, 2H); 6.92 (d, 1H, J ) 8.6 Hz); 7.26 (dd, 1H, J ) 2.0, 8.6 Hz); 8.06
(d, 1H, J ) 2.0 Hz). HRMS (EI+): calcd for M+, 508.2323; found,
508.2327.
Synthesis of 8-(3,4-Diaminophenyl)-2,6-diethyl-4,4-difluoro-
1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-Et) and
8-(3,4-Diaminophenyl)-2,6-diethoxycarbonyl-4,4-difluoro-1,3,5,7-tet-
ramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-CO2Et). DAMBO-
Et and DAMBO-CO2Et were prepared from 9a and 9b by the same
method as that used to obtain DAMBO, in 43% and 44% yield,
respectively.
Synthesis of 8-(4-Amino-3-nitrophenyl)-4,4-difluoro-2,6-bis-(2-
methoxycarbonylethyl)-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-in-
dacene (12). 12 was prepared from 11 by the same method as that
1
DAMBO-Et. Recrystallized from CHCl3/n-hexane to afford green
used to obtain DAMBO, in 31% yield. H NMR (CDCl3): δ 1.46 (s,
1
crystals. H NMR (CDCl3): δ 0.98 (t, 6H, J ) 7.5 Hz); 1.43 (s, 6H);
6H); 2.37 (t, 4H, J ) 7.3, 8.3 Hz); 2.54 (s, 6H); 2.65 (t, 4H, J ) 7.3,
8.3 Hz); 3.66 (s, 6H); 6.32 (s, 2H); 6.99 (d, 1H, J ) 8.4 Hz); 7.24 (dd,
1H, J ) 1.8, 8.4 Hz); 8.06 (d, 1H, J ) 1.8 Hz). HRMS (EI+): calcd
for M+, 556.2305; found, 556.2294.
2.30 (q, 4H, J ) 7.5 Hz); 2.51 (s, 6H); 3.46 (s, 2H); 3.52 (s, 2H); 6.57
(d, 1H, J ) 8.4 Hz); 6.59 (s, 1H); 6.78 (d, 1H, J ) 8.4 Hz). 13C NMR
(CDCl3): δ 11.8, 12.5, 14.6, 17.1, 116.4, 117.0, 120.1, 127.3, 131.2,
132.4, 135.1, 135.3, 138.6, 141.1, 153.1. HRMS (EI+): calcd for M+,
410.2453; found, 410.2446. Mp: 280-283 °C (dec). Anal. Calcd for
C23H29BF2N4‚0.1CHCl3: C, 65.71; H, 6.95; N, 13.27. Found: C, 66.09;
H, 6.65; N, 13.28.
DAMBO-CO2Et. Recrystallized from CHCl3/n-hexane to afford
green crystals. 1H NMR (CDCl3): δ 1.33 (t, 6H, J ) 7.1 Hz); 1.82 (s,
6H); 2.82 (s, 6H); 3.50 (s, 2H); 3.62 (s, 2H); 4.28 (q, 4H, J ) 7.1 Hz);
6.55 (dd, 1H, J ) 1.8, 8.3 Hz); 6.56 (d, 1H, J ) 1.8 Hz); 6.82 (d, 1H,
J ) 8.3 Hz). 13C NMR (CDCl3): δ 14.0, 14.3, 14.9, 60.2, 115.7, 117.2,
119.6, 122.2, 125.6, 131.9, 135.8, 136.2, 147.0, 147.9, 158.9, 164.5.
HRMS (EI+): calcd for M+, 498.2250; found, 498.2222. Mp: 241-
242 °C. Anal. Calcd for C25H29BF2N4O4‚0.5H2O: C, 59.18; H, 5.96;
N, 11.04. Found: C, 59.41; H, 5.75; N, 11.11.
Synthesis of 8-(5-Benzotriazolyl)-2,6-diethyl-4,4-difluoro-1,3,5,7-
tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-Et-T) and 8-(5-
Benzotriazolyl)-2,6-diethoxycarbonyl-4,4-difluoro-1,3,5,7-tetramethyl-
4-bora-3a,4a-diaza-s-indacene (DAMBO-CO2Et-T). DAMBO-Et-T
and DAMBO-CO2Et-T were prepared from DAMBO-Et and DAMBO-
CO2Et by a method similar to that used for DAMBO-T, in 20% and
85% yield, respectively.
Synthesis of 8-(4-Amino-3-nitrophenyl)-2,6-bis-(2-carboxyethyl)-
4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (13).
12 (183 mg, 0.33 mmol) was dissolved in 100 mL of MeOH, then 10
mL of 0.2 N NaOH was added, and the mixture was refluxed at 80 °C
for 1 h. The reaction mixture was evaporated and acidified with 2 N
HCl. The aqueous solution was extracted with ethyl acetate. The
combined organic extracts were dried over Na2SO4, filtered, and
evaporated. The crude compound was purified by column chromatog-
raphy over silica gel (CH2Cl2/ MeOH, 10:1) to afford an orange powder
1
(87 mg, yield 50%). H NMR (CD3OD): δ 1.44 (s, 6H); 2.26 (t, 4H,
J ) 7.3, 7.9 Hz); 2.40 (s, 6H); 2.57 (t, 4H, J ) 7.3, 7.9 Hz); 7.07 (d,
1H, J ) 8.6 Hz); 7.17 (dd, 1H, J ) 2.0, 8.6 Hz); 7.88 (d, 1H, J ) 2.0
Hz). HRMS (ESI+): calcd for [M+Na]+, 551.1889; found, 551.1922.
Synthesis of 8-(3,4-Diaminophenyl)-2,6-bis(2-carboxyethyl)-4,4-
difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-
PH). 13 (87 mg, 0.16 mmol) was dissolved in 100 mL of MeOH. After
the addition of 10% Pd-C (50 mg), the mixture was stirred vigorously
under a H2 atmosphere. When TLC monitoring (silica; CH2Cl2/ MeOH,
5:1) showed complete consumption of 13, the Pd-C was filtered off
and washed with MeOH. The residue after evaporation of the filtrate
was purified by column chromatography over silica gel (CH3CN/H2O,
10:1) and recrystallized from EtOH to afford orange needles (32 mg,
DAMBO-Et-T. Recrystallized from CHCl3/n-hexane to afford brown
1
needles. H NMR (CDCl3): δ 0.96 (t, 6H, J ) 7.5 Hz); 1.17 (s, 6H);
1
2.28 (q, 4H, J ) 7.5 Hz); 2.55 (s, 6H); 7.41 (d, 1H, J ) 8.6 Hz); 7.86
yield 38%). H NMR (CD3OD): δ 1.51 (s, 6H); 2.28 (t, 4H, J ) 7.1,
(br, 1H); 8.07 (br, 1H); 12.93 (br, 1H). MS (EI): 421 (M+). HRMS
8.4 Hz); 2.47 (s, 6H); 2.64 (t, 4H, J ) 7.1, 8.4 Hz); 6.46 (dd, 1H, J )
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3366 J. AM. CHEM. SOC. VOL. 126, NO. 10, 2004