S. Nakatani et al. / Bioorg. Med. Chem. 14 (2006) 5402–5422
5415
4.32. (2S)-4-{[4-(1-Benzofuran-2-yl)benzoyl]amino}-2-
[(benzyloxy)methoxy]butanoic acid (47a)
4.36. Ethyl 4-[(4-iodobenzoyl)amino]butanoate (49) and
ethyl 2-benzyl-4-[(4-iodobenzoyl)amino]butanoate (50)
The title compound was obtained as a white powder in
96% yield from 46a according to the same procedures
as described for the preparation of 29: TLC Rf = 0.45
The ester 49 was obtained as a white powder in 75%
yield from 48 according to the same procedures as de-
scribed for the preparation of 28. To a stirred solution
of 49 (410 mg, 1.14 mmol) in THF (10 mL) was added
dropwise LiHMDS (2.51 mL of a 1.0 M solution in
THF) at ꢀ78 °C. The reaction mixture was stirred for
1 h. After dropwise addition of benzyl bromide
(407 lL, 3.42 mmol), the reaction mixture was warmed
up to ꢀ30 °C, stirred for 3 h, quenched with saturated
NH4Cl, and extracted with EtOAc. The organic layer
was washed with brine and dried over Na2SO4. Removal
of the volatiles in vacuo provided a solid, which was
washed with Et2O–n-hexane to give 424 mg (82%) of
50 as a white powder: TLC Rf = 0.69 (EtOAc–n-hexane,
1:1); 1H NMR (200 MHz, DMSO-d6) d 8.53 (t,
J = 5.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.59 (d,
J = 8.4 Hz, 2H), 7.30–7.12 (m, 5H), 3.94 (q,
J = 7.0 Hz, 2H), 3.33–3.20 (m, 2H), 2.86–2.62 (m, 3H),
1.90–1.60 (m, 2H), 1.02 (t, J = 7.0 Hz, 3H).
1
(CHCl3–MeOH–H2O, 100:20:1); H NMR (200 MHz,
DMSO-d6)
d 8.61 (t, J = 5.4 Hz, 1H), 8.01 (d,
J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H), 7.70–7.63
(m, 2H), 7.57 (br s, 1H), 4.82 (d, J = 7.0 Hz, 1H), 4.77
(d, J = 7.0 Hz, 1H), 4.64 (d, J = 11.8 Hz, 1H), 4.54 (d,
J = 11.8 Hz, 1H), 4.13 (dd, J = 8.2, 4.2 Hz, 1H), 3.52–
3.28 (m, 2H), 2.12–1.82 (m, 2H).
4.33. (2R)-4-{[4-(1-Benzofuran-2-yl)benzoyl]amino}-2-
[(benzyloxy)methoxy]butanoic acid (47b)
The title compound was obtained as a white powder in
100% yield from 46b according to the same procedures
as described for the preparation of 29: TLC Rf = 0.45
1
(CHCl3–MeOH–H2O, 100:20:1); H NMR (200 MHz,
DMSO-d6)
d 8.61 (t, J = 5.4 Hz, 1H), 8.01 (d,
J = 8.8 Hz, 2H), 7.95 (d, J = 8.8 Hz, 2H), 7.70–7.63
(m, 2H), 7.57 (br s, 1H), 4.82 (d, J = 7.0 Hz, 1H), 4.77
(d, J = 7.0 Hz, 1H), 4.64 (d, J = 11.8 Hz, 1H), 4.54 (d,
J = 11.8 Hz, 1H), 4.13 (dd, J = 8.2, 4.2 Hz, 1H), 3.52–
3.28 (m, 2H), 2.12–1.82 (m, 2H).
4.37. Ethyl 4-{[4-(1-benzofuran-2-yl)benzoyl]amino}-2-
benzylbutanoate (51)
The title compound was obtained as an off-white pow-
der in 81% yield from 50 according to the same proce-
dures as described for the preparation of 26: TLC
4.34. 4-(1-Benzofuran-2-yl)-N-[(3S)-3-[(benzyloxy)meth-
oxy]-4-(hydroxyamino)-4-oxobutyl]benzamide (7)
1
Rf = 0.47 (EtOAc–n-hexane, 1:2); H NMR (200 MHz,
CDCl3): d 7.92 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz,
2H), 7.63–7.52 (m, 2H), 7.36–7.16 (m, 7H), 7.12 (br s,
1H), 6.41 (m, 1H), 4.05 (br q, J = 7.0 Hz, 2H), 3.62–
3.41 (m, 2H), 3.09–2.96 (m, 1H), 2.87–2.72 (m, 2H),
1.13 (t, J = 7.0 Hz, 3H).
The title compound was obtained as a white powder in
62% yield from 47a according to the same procedures
as described for the preparation of 2: TLC Rf = 0.24
(CHCl3–MeOH, 10:1); MS (APCI, neg. 40 V) m/z 473
(MꢀH)ꢀ; IR (KBr) 1627, 1539, 1497, 1450, 1310,
1
1108, 1065, 1032 cmꢀ1; H NMR (200 MHz, DMSO-
4.38. 4-{[4-(1-Benzofuran-2-yl)benzoyl]amino}-2-benzyl-
butanoic acid (52)
d6) d 10.75 (br s, 1H), 8.90 (br s, 1H), 8.55 (t,
J = 5.6 Hz, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.96 (d,
J = 8.8 Hz, 2H), 7.71–7.63 (m, 2H), 7.58 (br s, 1H),
7.39–7.24 (m, 7H), 4.77 (d, J = 7.0 Hz, 1H), 4.68 (d,
J = 7.0 Hz, 1H), 4.58 (s, 2H), 4.04 (t, J = 5.8 Hz, 1H),
The title compound was obtained as a white powder in
86% yield from 51 according to the same procedures as
described for the preparation of 29: TLC Rf = 0.37
(CHCl3–MeOH, 10:1); 1H NMR (200 MHz, DMSO-
d6) d 12.22 (br s, 1H), 8.58 (t, J = 5.6 Hz, 1H), 7.70–
7.63 (m, 2H), 7.57 (br s, 1H), 7.39–7.14 (m, 7H),
3.39–3.25 (m, 2H), 2.92–2.62 (m, 3H), 1.90–1.60 (m,
2H).
3.49–3.25 (m, 2H), 1.93 (q, J = 6.2 Hz, 2H); optical rota-
30
D
C27H27N2O6: 475.1869. Found: 475.1867.
tion ½aꢁ ꢀ27.0 (c 0.23, DMF); HRMS (FAB) calcd for
4.35. 4-(1-Benzofuran-2-yl)-N-[(3R)-3-[(benzyloxy)meth-
oxy]-4-(hydroxyamino)-4-oxobutyl]benzamide (8)
4.39. 4-(1-Benzofuran-2-yl)-N-[3-benzyl-4-(hydroxy-
amino)-4-oxobutyl]benzamide (9)
The title compound was obtained as a white powder in
61% yield from 47b according to the same procedures
as described for the preparation of 2: TLC Rf = 0.24
(CHCl3–MeOH, 10:1); MS (APCI, neg. 40 V) m/z 473
(MꢀH)ꢀ; IR (KBr) 1627, 1539, 1497, 1450, 1311,
The title compound was obtained as a white powder in
65% yield from 52 according to the same procedures as
described for the preparation of 2: TLC Rf = 0.39
(CHCl3–MeOH, 10:1); MS (MALDI, pos.) m/z 467
(M+K)+, 451 (M+Na)+, 429 (M+H)+; IR (KBr)
1655, 1636, 1607, 1560, 1497, 1451, 1308, 1257, 1200,
1
1108, 1065, 1031 cmꢀ1; H NMR (200 MHz, DMSO-
d6) d 10.75 (br s, 1H), 8.90 (br s, 1H), 8.55 (t,
J = 5.6 Hz, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.96 (d,
J = 8.8 Hz, 2H), 7.71–7.63 (m, 2H), 7.58 (br s, 1H),
7.39–7.24 (m, 7H), 4.77 (d, J = 7.0 Hz, 1H), 4.68 (d,
J = 7.0 Hz, 1H), 4.58 (s, 2H), 4.04 (t, J = 5.8 Hz, 1H),
1171, 1029 cmꢀ1 1H NMR (200 MHz, DMSO-d6) d
;
10.43 (s, 1H), 8.52 (t, J = 5.6 Hz, 1H), 8.00 (d,
J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.71–7.63
(m, 2H), 7.57 (s, 1H), 7.39–7.16 (m, 7H), 3.30–3.15
(m, 2H), 2.83 (dd, J = 13.6, 8.6 Hz, 1H), 2.66 (dd,
J = 13.6, 6.2 Hz, 1H), 2.44–2.31 (m, 1H), 1.88–1.53
3.49–3.25 (m, 2H), 1.93 (q, J = 6.2 Hz, 2H); optical rota-
30
D
C27H27N2O6: 475.1869. Found: 475.1872.
tion ½aꢁ +25.2 (c 0.23, DMF); HRMS (FAB) calcd for