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cross-coupling catalyst in 85% yield based on general
cross-coupling methods.12 Conversion of the ketones to
the amines 3b–e was accomplished through reduction
(NaBH4) followed by chlorination (SOCl2) and cyana-
tion (AgCN) to give the respective nitriles 7a–e. The
nitriles were subsequently reduced to the amines using
BH3–THF (Scheme 1).
5-Cyano-2-n-hexyl-10,11-dihydrodibenzo[a,d]cycloheptene
1
(7d). Yield (50%), oil. H NMR (CDCl3) d 1.30–1.35
(t, 3H, CH3), 1.51–2.29 (brm, 8H, CH2), 2.55–2.59 (t,
2H, CH2), 3.16–3.35 (m, 4H, CH2), 5.47 (s, 1H, CH),
7.13–7.49 (m, 8H, Ar-H); 13C NMR (CDCl3) d 26.66,
27.44, 27.98, 28.83, 29.97, 30.47, 32.33, 41.45, 124.67,
127.40, 128.06, 129.22, 131.19, 133.80, 138.82.
General method for the synthesis of 2-substitited-5-
cyano-10,11-dihydrodibenzo[a,d]cycloheptenes.
5-Cyano-2-methoxy-10,11-dihydrodibenzo[a,d]cycloheptene
(7e). Yield (96%), mp 106–107 ꢀC. (CHCl3-pet.ether).
2-(sub-
stituted)-10,11-dihydro-dibenzo[a,d]cyclohepten-5-one
(2.0 mmol) was dissolved in anhydrous CH3OH (15 mL)
and cooled (0 ꢀC). NaBH4 (10.0 mmol) was added in
portions and the reaction mixture brought to room
temperature and heated at reflux (1 12 h). The solvent was
removed under reduced pressure, water (20 mL) added
to the residue and the resulting solution was acidified
(dil HCl) to pH 4.0 and extracted with EtOAc (3Â50
mL). The combined EtOAc extracts were washed with
water, brine, and dried (MgSO4). The solvent was
removed under reduced pressure to give an oil which
was dissolved in anhydrous C6H6 (15 mL). SOCl2 (10.0
mmol) was added dropwise with stirring and the reac-
tion mixture was heated at reflux (11/2 h) and cooled.
The solvent was removed under reduced pressure to give
a brown oil which was redissolved in anhydrous C6H6
(10 mL) and added dropwise to a suspension of AgCN
(2.5 mmol) in anhydrous C6H6 (20 mL). The reaction
mixture was heated at reflux overnight, cooled and filtered.
The residue was washed with CH2Cl2 and the filtrate was
evaporated to dryness under reduced pressure to give a
dark brown oil. The oil was purified by mplc using pet-
roleum ether–EtOAc (9:1) as eluent.
lit.13 mp 87–88 ꢀC. H NMR (CDCl3) d 3.16–3.36 (m,
1
4H, CH2), 3.78 (s, 3H, OCH3), 5.39 (s, 1H, CH), 6.73–
7.48 (m, 7H, Ar-H); 13C NMR (CDCl3) d 32.30, 32.68,
40.91, 55.86, 112.25, 116.83, 126.02, 127.40, 128.12,
129.17, 129.58, 131.17, 134.21, 139.02, 140.39. Anal.
(C17H15NO): C, H, N.
General method for the synthesis of 5-aminomethyl-2-
(substituted)-10,11-dihydrodibenzo[a,d]cycloheptenes. 2-
(Substituted)-5-cyano-10,11-dihydrodibenzo-[a,d]cyclo-
heptene (1.0 mmol) was dissolved in anhydrous THF (1
mL) and cooled (0 ꢀC). Borane–THF complex (1.0 M
soln., 5.1 mmol) was added dropwise with stirring and
the mixture was slowly warmed to room temperature
and then heated at reflux (8 h). The reaction mixture
was cooled and HCl (6.0 M, 3 mL) was added dropwise
and the mixture was heated at reflux for another hour,
cooled and the solvent was removed under reduced
pressure. Water (20 mL) was added to the residue and
extracted with EtOAc (20 mL). The aqueous portion
was made basic with 10% NaOH and extracted with
Et2O (3Â25 mL). The combined Et2O extracts were
washed with water, brine, dried (MgSO4) and evapo-
rated under reduced pressure to give a brown oil which
was purified by mplc using CH2Cl2–CH3OH (9.5:0.5) as
eluent. The products were isolated as their respective
salts by treatment with either oxalic or fumaric acid in
anhydrous acetone.
2-Bromo-5-cyano-10,11-dihydrodibenzo[a,d]cycloheptene
ꢀ
1
(7b). Yield (84%), mp 68–69 C. H NMR (CDCl3) d
3.13–3.28 (bm, 4H, CH2), 5.41 (s, 1H, CH), 7.13–7.47
(m, 7H, Ar-H); 13C NMR (CDCl3): d 31.95, 32.14,
40.88, 119.22, 123.05, 127.61, 127.94, 129.46, 129.46,
129.64, 130.37, 131.20, 134.00, 138.41, 140.91.
5-Aminomethyl-2-bromo-10,11-dihydrodibenzo[a,d]cyclo-
heptene fumarate (3b). Yield (82%), mp 204–205 ꢀC
(EtOAc-CH3OH). 1H NMR (DMSO-d6) d 2.95–3.32
(brm, 6H, CH2), 4.36 (brs, 1H, CH), 6.43 (s, 2H, CH),
7.14-7.38 (m, 7H, Ar-H); 13C NMR (DMSO-d6) d 32.33,
32.43, 120.30, 126.63, 127.42, 129.19, 130.77, 132.98,
135.93, 142.84, 169.19. Anal. (C16H16NBr 0.50
C4H4O4): C, H, N.
5-Cyano-2-(3-phenylpropyl)-10,11-dihydrodibenzo[a,d]-
1
cycloheptene (7c). Yield (66%), oil. H NMR (CDCl3)
d 1.97–2.05 (m, 2H, CH2), 2.64–2.74 (m, 4H, CH2),
3.22–3.42 (m, 4H, CH2–CH2), 5.48 (s, 1H, CH), 7.06–
7.58 (m, 7H, Ar-H); 13C NMR (DMSO-d6) d 32.41,
32.50, 33.42, 35.51, 36.08, 41.23, 119.99, 126.49, 127.44,
128.08, 128.17, 128.28, 129.01, 129.11, 129.23, 131.19,
131.28, 131.46, 134.18, 138.73, 142.73, 143.48.
5-Aminomethyl-2-(3-phenylpropyl)-10,11-dihydrodibenzo
[a,d]cycloheptene fumarate (3c). Yield. (62%), mp 159–
160 ꢀC (EtOAc–CH3OH). 1H NMR (DMSO-d6) d 1.78–
1.86 (m, 2H, CH2), 2.49–2.60 (m, 4H, CH2), 2.96–3.26
(m, 4H, CH2–CH2), 3.40–3.42 (d, J=6 Hz, 2H, CH2),
4.40 (bs, 1H, CH), 6.48 (s, 2H, CH), 6.94-7.29 (m, 7H,
Ar-H); 13C NMR (DMSO-d6) d 32.64, 32.83, 34.57,
35.18, 39.06, 126.07, 126.49, 126.63, 127.56, 128.64,
.
130.78, 135.33, 141.13, 168.10. Anal. (C25H27N
C4H4O4) : C, H, N.
5-Aminomethyl-2-n-hexyl-10,11-dihydrodibenzo[a,d]cyclo-
heptene fumarate (3d). Yield (64%), mp 170–171 ꢀC
(EtOAc–CH3OH). 1H NMR (DMSO-d6) d 0.81–0.85 (t,
J=6 Hz, 2H, CH2), 1.17–1.50 (brm, 6H, CH2), 2.45–2.50
Scheme 1. (a) AlCl3, C6H6; (b) (CF3SO)2O, C5H5N; (c) 9-BBN, allyl-
benzene, PdCl2(dppf), K3PO4, THF; (d) 9-BBN, 1-hexene,
PdCl2(dppf), K3PO4, THF; (e) NaBH4, CH3OH; (f) SOCl2, C6H6; (g)
AgCN, C6H6; (h) BH3–THF, 6.0 M HCl.