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tography on silica gel (CH2Cl2/CH3OH, 99:1!19:1) to yield a color-
less solid (237 mg, 0.446 mmol, 51%). 1H NMR (400 MHz, CDCl3):
d=9.08 (s, 2H; guanidine NH2), 7.17 (t, J=5.9 Hz, 1H; NH), 6.96 (s,
1H; H2), 6.89 (d, J=8.2 Hz, 1H; H6), 6.60 (d, J=8.2 Hz, 1H; H5),
5.13 (s, 2H; NH2), 4.01 (t, J=7.7 Hz, 2H; H10), 3.90 (d, J=5.9 Hz,
2H; Bn CH2), 2.74 (t, J=7.0 Hz, 2H; H9), 1.49 (s, 9H; 3ꢂBoc CH3),
1.41 (s, 9H; 3ꢂBoc CH3), 1.37 ppm (s, 9H; 3ꢂBoc CH3); 13C NMR
(101 MHz, CDCl3): d=162.8 (C11), 159.4 (Boc C=O), 155.6 (Boc C=
O), 153.9 (Boc C=O), 148.1 (C4), 130.4 (C2), 128.3 (C6), 127.3 (C1),
113.6 (C5), 106.0 (C3), 91.4 (C8), 83.7 (Boc C(CH3)), 79.0 (C7), 77.8
(Boc C(CH3)), 77.6 (Boc C(CH3)), 43.2 (C10), 42.7 (Bn CH2), 28.3 (Boc
C(CH3)), 28.0 (Boc C(CH3)), 27.5 (Boc C(CH3)), 19.2 ppm (C9); TLC:
Rf =0.55 (CH2Cl2/CH3OH, 9:1); IR (neat): n˜ =3373, 2976, 1709, 1608,
1502, 1365, 1245, 1141, 1004, 744 cmꢀ1; HRMS (ESI+): m/z calcd:
532.3135 [M+H]+; found: 532.3136.
CH2). 44.2 (C9), 28.5 (Boc C(CH3)3), 28.1 (C8), 27.5 (Boc C(CH3)3),
21.4 ppm (Tos CH3); TLC: Rf =0.42 (petroleum ether 50–70/EtOAc,
2:1); IR (neat): n˜ =3378, 2931, 1709, 1607, 1504, 1471, 1443, 1365,
1282, 1162, 811, 545 cmꢀ1; HRMS (FAB): m/z calcd: 686.3 [M+H]+;
found: 686.5.
Method b: The reaction was performed according to general pro-
cedure 1 by using 29b (399 mg, 0.897 mmol) to yield a pale-yellow
oil (585 mg, 0.853 mmol, 95%). The analytical data were identical
to those reported above.
5-(O-tert-Butoxycarbonyl)aminomethyl-2-(2-N,N’-bis-tert-butoxy-
carbonylguanidinoethyl)-1H-indole (30a): Method a: The reaction
was carried out under a nitrogen atmosphere. A solution of 30b
(59 mg, 86 mmol) in dry methanol (3 mL) was mixed with NaOH
(600 mg, 15 mmol). The viscose reaction mixture was stirred at
room temperature for 40 h. After dilution with EtOAc, the solution
was washed with H2O (3ꢂ). The aqueous phase was extracted with
EtOAc and the combined organic layers were dried over sodium
sulfate. After removal of the solvent, the crude product was puri-
fied by column chromatography on silica gel (CH2Cl2/CH3OH,
5-(O-tert-Butoxycarbonyl)aminomethyl-2-(2-hydroxyethyl)-1-N-
(4-methylphenylsulfonyl)indole (29b): The reaction was per-
formed according to general procedure 2 by using 24b (500 mg,
0.995 mmol), 25 (3 equiv), and dry DMF (10 mL). A CH2Cl2/CH3OH
gradient from 99:1 to 19:1 was used for the column chromatogra-
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phy to yield a pale-yellow oil (399 mg, 0.898 mmol, 90%). H NMR
(400 MHz, CDCl3): d=7.94 (d, J=8.2 Hz, 1H; H7), 7.66 (d, J=8.2 Hz,
2H; H2’, H6’), 7.34 (d, J=8.1 Hz, 3H; H3’, H5’, NH), 7.30 (s, 1H; H4),
7.14 (d, J=8.7 Hz, 1H; H6), 6.59 (s, 1H; H3), 4.77 (t, J=5.5 Hz, 1H;
OH), 4.15 (d, J=5.9 Hz, 2H; Bn CH2), 3.76 (dt, J=6.4, 9.5 Hz, 2H;
H9), 3.14 (t, J=6.6 Hz, 2H; H8), 2.30 (s, 3H; Tos CH3), 1.38 ppm (s,
9H; 3ꢂBoc CH3); 13C NMR (101 MHz, CDCl3): d=156.1 (Boc C=O),
144.9 (C4’), 138.9 (C2), 134.4 (C7a), 130.4 (C3’, C5’), 129.4 (C3a),
126.0 (C2’, C6’), 122.8 (C5), 119.2 (C4), 110.1 (C3), 75.2 (Boc C(CH3)3),
59.5 (C9), 43.0 (Bn CH2), 32.2 (C8), 28.4 (Boc C(CH3)3), 21.3 ppm (Tos
CH3); TLC: Rf =0.37 (CH2Cl2/CH3OH, 19:1); IR (neat): n˜ =3400, 3054,
2977, 2930, 1510, 1469, 1364, 1090, 961, 670 cmꢀ1; HRMS (ESI+): m/
z calcd: 467.1617 [M+Na]+; found: 467.1615.
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19:1!9:1) to yield a colorless solid (43 mg, 82 mmol, 95%). H NMR
(400 MHz, CDCl3): d=10.94 (s, 1H; NH1), 7.27 (brs, 2H; H4, Boc
NH), 7.22 (d, J=8.2 Hz, 1H; H7), 6.92 (d, J=8.2 Hz, 1H; H6), 6.17 (s,
1H; H3), 4.15 (d, J=6.3 Hz, 1H; Bn CH2), 3.52 (t, J=7.9 Hz, 2H; H9),
2.90 (brs, 2H; H8), 1.42 (s, 9H; 3ꢂBoc CH3), 1.38 (s, 9H; 3ꢂBoc
CH3), 1.29 ppm (s, 9H; 3ꢂBoc CH3); 13C NMR (101 MHz, CDCl3): d=
160.9 (C10), 155.7 (2ꢂBoc C=O), 136.9 (C2), 135.1 (C7a), 130.4 (C5),
128.1 (C3a), 120.2 (C6), 117.7 (C4), 110.4 (C7), 99.0 (C3), 77.5 (C9),
44.0 (Bn CH2), 28.3 (2ꢂBoc C(CH3)), 28.1 ppm (C8); TLC: Rf =0.28
(CH2Cl2/CH3OH, 9:1); IR (neat): n˜ =3281, 2930, 1683, 1632, 1486,
1390, 1146, 966, 776 cmꢀ1; HRMS (FAB): m/z calcd: 532.3135 [M+
H]+; found: 532.3122.
N,N’-Bis-tert-Butoxycarbonylguanidinobut-3-yne (27): The reac-
tion was performed according to general procedure 1 by using 25
(0.38 mL, 5.0 mmol) to yield a colorless solid (1.36 g, 4.37 mmol,
Method b: The reaction was carried out under a nitrogen atmos-
phere. KH (19 mg, 0.48 mmol, 1.2 equiv) was added to a suspension
of 28b (214 mg, 0.402 mmol) and Cu(OAc)2 (80 mg, 0.44 mmol,
1.1 equiv) in dry 1,2-dichloroethane (11 mL). After that, the reaction
mixture was stirred at 708C for 4 d. The crude product was purified
by column chromatography on silica gel (CH2Cl2/CH3OH, 99:1!9:1)
to yield a pale-yellow solid (123 mg, 0.230 mmol, 57%). The analyt-
ical data were identical to those reported above.
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87%). H NMR (400 MHz, CDCl3): d=9.06 (s, 2H; NH2), 3.90 (t, J=
8.3 Hz, 2H; H1), 2.89 (t, J=2.5 Hz, 1H; H4), 2.44 (dt, J=8.1, 2.9 Hz,
2H; H2), 1.50 (s, 9H; 3ꢂBoc CH3), 1.41 ppm (s, 9H; 3ꢂBoc CH3);
13C NMR (101 MHz, CDCl3): d=160.9 (C5), 154.8 (2ꢂBoc C=O), 83.0
(C3), 80.0 (2ꢂBoc C(CH3)3), 73.3 (C4), 43.4 (C1), 28.4 (2ꢂBoc
C(CH3)3), 18.3 ppm (C2); TLC: Rf =0.42 (petroleum ether 50–70/
EtOAc, 2:1); IR (neat): n˜ =3376, 3197, 2984, 2965, 1637, 1512, 1450,
1308, 1120, 1003, 597 cmꢀ1; MS (FAB): m/z calcd: 312.2 [M+H]+;
found: 312.3.
2-(2-Guanidinoethyl)-5-aminomethyl-1H-indole (10): In a 25 mL
round-bottomed flask, 30a (55 mg, 0.10 mmol) was dissolved in
CH3CN/2m HCl (1:1; 8 mL). After the reaction mixture had been
stirred at room temperature for 28 h, the solvent was removed
under reduced pressure. The crude product was purified by
column chromatography on RP silica gel with H2O as the eluent.
Freeze drying of the product fractions yielded a pale-rose solid of
10 as the hydrochloride salt (22 mg, 73 mmol, 73%). 1H NMR
(400 MHz, CDCl3): d=11.37 (s, 1H; NH1), 8.33 (s, 3H; Bn NH2, guani-
dine NH), 7.86 (t, J=5.8 Hz, 1H; guanidine NH), 7.54 (s, 1H; H4),
7.32 (d, J=8.7 Hz, 1H; H7), 7.13 (dd, J=8.3, 1.7 Hz, 1H; H6), 6.27
(s, 1H; H3), 4.01 (dt, J=5.8, 5.8 Hz, 2H; Bn CH2), 3.52 (dt, J=6.9,
6.3 Hz, 2H; H9), 2.94 ppm (t, J=7.3 Hz, 2H; H8); 13C NMR
(101 MHz, CDCl3): d=156.9 (C10), 136.9 (C2), 135.4 (C7a), 127.9
(C3a), 123.8 (C5), 120.8 (C6), 120.4 (C4), 110.7 (C7), 99.1 (C3), 58.7
(C9), 42.6 (Bn CH2), 28.8 ppm (C8); IR (neat): n˜ =3326, 3232, 3052,
2923, 1683, 1486, 1309, 1164, 967, 804, 641 cmꢀ1; HRMS (FAB): m/z
calcd: 232.1557 [M+H]+; found: 232.1552.
5-(O-tert-Butoxycarbonyl)aminomethyl-2-(2-N,N’-bis-tert-butoxy-
carbonylguanidinoethyl)-1-N-(4-methylphenylsulfonyl)indole
(30b): Method a: The reaction was performed according to general
procedure 2 by using 24b (254 mg, 0.506 mmol), 27 (3 equiv), and
dry DMF (7 mL). A petroleum ether 50–70/EtOAc gradient from 4:1
to 1:1 was used for the column chromatography to yield a pale-
yellow oil (212 mg, 0.309 mmol, 62%). 1H NMR (400 MHz, CDCl3):
d=9.12 (s, 2H; NH2), 8.01 (d, J=8.6 Hz, 1H; H7), 7.71 (d, J=8.2 Hz,
2H; H2’, H6’), 7.37–7.30 (m, 3H; H3’, H5’, NH), 7.29 (s, 1H; H4), 7.18
(dd, J=8.8, 1.2 Hz, 1H; H6), 6.50 (s, 1H; H3), 4.20 (t, J=6.3 Hz, 2H;
H9), 4.14 (d, J=5.9 Hz, 2H; Bn CH2), 3.23 (t, J=5.8 Hz, 2H; H8),
2.30 (s, 3H; Tos CH3), 1.41 (s, 9H; 3ꢂBoc CH3), 1.38 (s, 9H; 3ꢂBoc
CH3), 1.19 ppm (s, 9H; 3ꢂBoc CH3); 13C NMR (101 MHz, CDCl3): d=
160.0 (Boc C=O), 156.1 (Boc C=O), 154.5 (C10), 145.6 (C4’), 138.8
(C2), 135.5 (C3a), 135.5 (C1’), 130.5 (C3’, C5’), 130.0 (C7a), 129.9
(C5), 126.3 (C2’, C6’), 123.9 (C6), 119.0 (C4), 114.3 (C7), 110.8 (C3),
84.7 (Boc C(CH3)3), 83.9 (Boc C(CH3)3), 78.3 (Boc C(CH3)3), 43.6 (Bn
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