Molecules 2017, 22, 690
9 of 13
3
.5. Synthesis of Compound 3b
To a stirred solution of 12 (35 mg, 0.06 mmol) in acetone (1.5 mL) was added 2-aminothiazole
◦
(
(
18 mg, 0.18 mmol). The mixture was stirred at 50 C for 20 h, then DCM (20 mL) and NaHCO
3
aq.) (10 mL) were added. And the mixture was stirred for another 30 min at room temperature.
3). The organic layer was collected,
dried over Na SO and concentrated. The residue was purified through a silica chromatography
Then the aqueous layer was extracted with DCM (5 mL
×
2
4
column (CHCl3 MeOH
−
Et N 25:1:0.2) to afford the product (3b) as a white solid (20 mg, 55.0%).
−
3
1
H-NMR (500 MHz, C D N):
δ
6.25 (1H, d, J = 5.0 Hz, H of thiazolimine), 5.96 (1H, d, J = 5.0 Hz, H of
),
.33 (1H, d, J = 10.5 Hz, H-18), 1.24 (3H, s, CH ), 0.99 (3H, s, CH ), 0.94 (9H, br s, 3CH ), 0.85 (3H, s,
5
5
thiazolimine), 5.44 (1H, br s, H-12), 4.83 (2H, q, J = 10.2 Hz, CH ), 4.75 (1H, dd, J = 5.0, 12.0 Hz, H-3
α
2
3
3
3
3
13
CH ), 0.77 (3H, s, CH ). C-NMR (125 MHz, C D N):
δ 180.3, 168.9, 163.0, 144.9, 128.3, 122.3, 97.4,
3
3
5
5
8
2
2.1, 55.4, 47.8, 47.3, 46.7, 46.5, 42.1, 42.0, 39.7, 38.1, 38.0, 37.1, 34.2, 33.3, 33.2, 33.0, 31.0, 28.3, 28.2, 26.2,
3.8, 23.7, 23.7, 18.4, 17.4, 16.9, 15.3. ESI-MS: m/z [M − H] 595.5.
−
3
.6. Synthesis of Compound 13
To a stirred solution of
4
(40 mg, 0.07 mmol) in DCM (1 mL) was added 2c (55 mg, 0.29 mmol),
◦
EDCI (70 mg, 0.37 mmol) and DMAP (5 mg, 0.04 mmol). The mixture was stirred at 50 C for 4 h. Then
the reaction solution was concentrated. The residue was purified through a silica chromatography
column (petroleum ether
H-NMR (300 MHz, CDCl ):
−
EtOAc 20:1) to afford the product (13) as white solid (41 mg, 78.0%).
7.78 (2H, d, J = 7.5 Hz, H-2, 6 of Ph) 7.42 (3H, m, H-3, 4, 5 of Ph), 7.34
1
δ
3
(
5
1
5H, s, Bn), 7.10 (1H, d, J = 1.8 Hz, H of furan), 6.73 (1H, d, J = 1.8 Hz, H of furan), 5.30 (1H, br s, H-12),
.08 (2H, ABq, J = 12.0 Hz, CH of Bn), 4.72 (1H, t, J = 8.7 Hz, H-3 ), 2.91 (1H, d, J = 12.9 Hz, H-18),
.14 (3H, s, CH ), 0.99 (3H, s, CH ), 0.95 (6H, br s, 2CH ), 0.92 (3H, s, CH ), 0.90 (3H, s, CH ), 0.63 (3H,
α
2
3
3
3
3
3
+
s, CH ). ESI-MS: m/z [M + Na] 739.6.
3
3
.7. Synthesis of Compound 3c
To a stirred solution of 13 (41 mg, 0.057 mmol) in a mixed solvent of MeOH (0.4 mL) and
DCM (0.1 mL) was added 10% Pd/C (4 mg) and H . The mixture was stirred for 20 h at room
2
temperature, then filtered and the filtrate was concentrated. The residue was purified through a
silica chromatography column (petroleum ether
solid (29 mg, 89.6% based on 4 mg recovery of substrate). H-NMR (300 MHz, CDCl ):
−
acetone 15:1) to afford the product (3c) as a white
1
δ 7.78 (2H,
3
d, J = 7.5 Hz, H-2, 6 of Ph), 7.41 (2H, t, H-3, 5 of Ph), 7.33 (1H, t, H-4 of Ph),7.20 (1H, d, J = 3.3 Hz,
H of furan), 6.73 (1H, d, J = 3.6 Hz, H of furan), 5.29 (1H, br s, H-12), 4.74 (1H, t, H-3 ), 2.83 (1H, d,
J = 10.5 Hz, H-18), 1.16 (3H, s, CH ), 1.00 (6H, br s, 2CH ), 0.96 (3H, s, CH ), 0.94 (3H, s, CH ), 0.92
α
3
3
3
3
13
(
3H, s, CH ), 0.78 (3H, s, CH ). C-NMR (75 MHz, CDCl3): δ 184.1, 158.7, 157.4, 144.1, 143.6, 129.6,
3 3
1
3
28.8 (3C), 124.8 (2C), 122.6, 119.4, 106.7, 81.5, 55.3, 47.5, 46.5, 45.8, 41.6, 40.9, 39.3, 38.1, 37.0, 33.8, 33.1,
−
2.5, 32.4, 30.7, 28.2, 27.7, 25.9, 23.6, 23.4, 22.9, 18.2, 17.2, 16.8, 15.4. ESI-MS: m/z [M − H] 625.5.
.8. Synthesis of Compound 16
3
To a stirred solution of
4 (10 mg, 0.018 mmol) in DCM (0.4 mL) was added 2d (6 mg, 0.036 mmol),
DCC (14.8 mg, 0.072 mmol) and DMAP (0.2 mg, 0.0018 mmol). The mixture was stirred for 2 h at
room temperature. Then the precipitate was filtered and the filtrate was concentrated. The residue
was purified through a silica chromatography column (petroleum ether
−
EtOAc 20:1) to afford the
1
product (16) as a white solid (8 mg, 63.0%). H-NMR (300 MHz, CDCl ):
δ 7.29 (5H, s, Bn), 7.24 (1H, s,
3
H-4 of pyrazole), 5.96 (1H, s, H-5 of pyrazole), 5.28 (1H, br s, H-12), 5.12–5.02 (2H, ABq, J = 12.6 Hz,
CH of Bn), 4.48 (1H, t, J = 8.1 Hz, H-3 ), 4.36 (1H, dd, -N-CH2-CH-, J = 6.9, 13.5 Hz), 4.03 (1H,
-COOH), 2.90 (1H, d, J = 9.6 Hz, H-18), 2.25 (3H, s, CH of
α
2
m, -N-CH2-CH-), 3.08 (1H, m, -CH -C
H
2
3
pyrazole), 1.16 (3H, d, CH3-CH-COOH), 1.12 (3H, s, CH ), 0.91 (3H, s, CH ), 0.89 (6H, br s, 2CH ), 0.82
3
3
3
+
(
6H, br s, 2CH ), 0.60 (3H, s, CH ). ESI-MS: m/z [M + H] 697.8.
3 3