19 We employed the Cbz-derivative 14 as the Cbz protecting group can be removed
under mild conditions, whereas it was found the acid or base needed
to remove either the tert-butyloxycarbonyl
(Boc) or fluorenylmethyloxycarbonyl (Fmoc) protecting groups degraded
the unmasked amino aldehyde 13. Full details
will be reported in due course.
22 (S)-Benzyl
1-(indol-3-yl)-3-oxopropan-2-ylcarbamate (14):²¹ To
a stirred solution of Weinreb amide 15 (416
mg, 1.1 mmol) in Et2O (60 mL) was added LiAlH4 (209
mg, 5.5 mmol) at 0 ˚C and the reaction mixture was stirred
for 2 h at this temperature. The reaction mixture was quenched with H2O
(10 mL), filtered through Celite® and the cake
was washed with H2O (40 mL) and then with Et2O
(20 mL). The filtrate was extracted with Et2O (3 × 30
mL) and the combined organic layers were washed with HCl acid (1
M, 3 × 30 mL), sat. NaHCO3 solution (3 × 30
mL), brine (30 mL), dried (MgSO4), filtered and concentrated
in vacuo. Purification by flash chromatography using EtOAc-hexanes (1:1, R
f
0.5)
as eluent gave the title compound (320 mg, 0.99 mmol, 90%)
as a yellow oil; [α]D
²¹ +30.1
(c = 1.0, CH2Cl2). IR
(neat): 3347, 2924, 1704, 1456, 1513, 1373, 1341, 1244, 1045, 845,
744, 698 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 2.91
(m, 1 H, CHβ
H
βCHα),
3.21 (m, 1 H, CH
βHβCHα), 4.25
(s, 1 H, CHα), 5.03 (m, 2 H, CH
2Ph),
6.96 (t, J = 6.8 Hz, 1 H, ArH),
7.08 (m, 1 H, ArH), 7.16 (s, 1 H, ArH), 7.33 (m, 6 H, ArH), 7.54
(d, J = 8.0 Hz, 1 H, ArH), 7.73
(d, J = 7.6 Hz, 1 H, NH), 9.59
(s, 1 H, CHO), 10.86 (s, 1 H, NH). ¹³C NMR
(100 MHz, DMSO-d
6): δ = 23.7
(CH2), 60.4 (CH), 65.5 (CH2), 109.5 (C), 111.3
(CH), 118.1 (CH), 118.3 (CH), 120.9 (CH), 123.7 (CH), 127.6 (CH),
127.7 (2 × CH), 128.2 (CH), 128.3 (2 × CH), 136.1
(C), 136.8 (C), 156.1 (CONH), 201.2 (CHO). MS: m/z (ESI+, %) = 323
(30) [M + H]+, 305 (65),
261 (30), 130 (10), 91 (3). HRMS: m/z [M + H]+ calcd for
C19H18N2O3 + H:
323.1380; found: 323.1383.
23 2,5-Bis(indol-3-ylmethyl)pyrazine
(11):¹¹,²4 To
a solution of aldehyde 14 (85 mg, 0.26
mmol) in MeOH-CH2Cl2-AcOH (2:2:1,
5 mL) was added Pearlman’s catalyst [Pd(OH)2,
20% on carbon, ca.10 mg] and the reaction mixture
was stirred under an atmosphere of hydrogen for 2 h. The hydrogen balloon
was removed and the reaction mixture was stirred for a further 15
h while open to the air, filtered through Celite® and
the filtrate was concentrated in vacuo. Purification by flash chromatography
using EtOAc-hexanes (1:1, R
f
0.46) as eluent gave the title
compound (32 mg, 0.095 mmol, 73%) as a colorless oil. IR
(neat): 3223, 2955, 2912, 2850, 1659, 1493, 1458, 1375, 1343, 1259,
1095, 1044, 970, 922, 797, 732, 589 cm-¹.
For ¹H NMR and ¹³C NMR
data see, Table
[¹]
.
MS: m/z (ESI+, %) = 339
(100)
[M + H]+,
282 (20), 242 (15), 157 (2). HRMS: m/z [M + H]+ calcd
for C22H18N4 + H: 339.1604;
found: 339.1593.
24 See Supplementary Information for ¹H
NMR and ¹³C NMR spectra of synthetic 11.
