J 8.8 Hz, CONH), 7.89 (1H, d, J 8.7 Hz, CONH), 7.37–7.26
(5H, m, 5 × aryl-H), 5.78–5.71 (1H, m, CONHCH), 5.62–5.55
(1H, m, CONHCH), 4.62 (1H, d, J 12.3 Hz, CH2OCHaHbPh),
4.58 (1H, d, J 12.3 Hz, CH2OCHaHbPh), 4.30–3.93 (4H, m,
CH2OTBS, CH2OBn), 2.81 (3H, s, oxazole-CH3), 2.74 (3H, s,
oxazole-CH3), 0.90 (9H, s, SiC(CH3)3), −0.08 (3H, s, SiCH3(CH3))
and −0.03 (3H, s, SiCH3(CH3)) ppm; m/z (ESI) found: 831.2527,
C39H40N8O10SiNa [(M + Na)+] requires 831.2534.
(80 mL) and saturated sodium bicarbonate solution (80 mL). The
aqueous extract was re-extracted with dichloromethane (80 mL)
and the combined organic extracts were dried (MgSO4) and then
concentrated in vacuo. The solid yellow residue was purified by
chromatography on silica gel using 6 : 1 dichloromethane–ether
as eluent◦to give the thioamide (0.23 g, 50%) as a colourless solid;
mp 151 C (decomp.) (from dichloromethane–petrol); [a]2D2 +74
(c = 1.0, CHCl3); mmax(CHCl3)/cm−1 3449, 3345, 2930, 1719, 1653
and 1585; dH(360 MHz, CDCl3) 9.46 (1H, d, J 8.1 Hz, CSNH),
8.43 (1H, s, oxazole-H), 8.34 (1H, s, oxazole-H), 8.32 (1H, s,
oxazole-H), 8.03–7.99 (2H, m, 2 × phenyloxazole-H), 7.48–7.42
(3H, m, 3 × phenyloxazole-H), 6.14–6.09 (1H, m, CSNHCH),
5.30 (1H, br s, BocNH), 4.55 (2H, d, J 5.9 Hz, BocNHCH2), 4.33
(1H, dd, J 10.2 and 4.1 Hz, CHaHbOTBS), 4.19 (1H, dd, J 10.2
and 5.0 Hz, CHaHbOTBS), 3.93 (3H, s, CO2CH3), 1.46 (9H, s,
OC(CH3)3), 0.86 (9H, s, SiC(CH3)3), 0.06 (3H, s, SiCH3(CH3))
and 0.03 (3H, s, SiCH3(CH3)) ppm; dC(90 MHz, CDCl3) 185.3 (s),
162.8 (s), 162.3 (s), 159.3 (s), 156.1 (s), 155.9 (s), 154.1 (s), 142.8
(d), 142.0 (s), 139.7 (d), 139.1 (d), 130.9 (s), 130.4 (d), 129.7 (s),
128.4 (d), 128.4 (d), 126.9 (s), 126.6 (s), 80.4 (s), 63.4 (t), 53.7 (d),
52.3 (q), 37.9 (t), 28.2 (q), 25.6 (q), 18.1 (s) and −5.5 (q) ppm; m/z
(ESI) found: 773.2461, C35H42N6O9SSiNa [(M + Na)+] requires
773.2401.
2-[(S)-1-{[2ꢀꢀ-(tert-Butoxycarbonylaminomethyl)-[2,4ꢀ;2ꢀ,4ꢀꢀ]-
teroxazole-4-carbonyl]-amino}-2-(tert-butyldimethylsilanyloxy)-
ethyl]-5-phenyloxazole-4-carboxylic acid methyl ester (64)
4-Methylmorpholine (0.77 mL, 7.0 mmol) was added to a
stirred suspension of the acid 63b (0.26 g, 0.70 mmol) and 1-
hydroxybenzotriazole (0.47 g, 3.5 mmol) in dry dichloromethane
(10 mL) and N,N-dimethylformamide (5 mL) at
0
◦C
under a nitrogen atmosphere. 1-[3-(Dimethylamino)propyl]-3-
ethylcarbodiimide hydrochloride (0.27 g, 1.4 mmol) was added
◦
and the mixture was then stirred at 0 C for 10 min. A solution
of the amine 60 (0.28 g, 0.74 mmol) in dry dichloromethane
◦
(5 mL) was added dropwise over 3 min at 0 C, and the mixture
was allowed to warm to room temperature overnight and then
quenched with water (20 mL). Dichloromethane (30 mL) was
added and the separated organic layer was washed with 10%
aqueous citric acid (2 × 15 mL) and saturated sodium bicarbonate
solution (15 mL), then dried (MgSO4) and concentrated in vacuo.
The residue was purified by chromatography on silica gel using
1 : 1 dichloromethane–ethyl acetate as eluent to give the tetra-
4-[(S)-2-Hydroxy-1-(4-methoxycarbonyl-5-phenyloxazol-2-yl)-
ethylthiocarbamoyl]-[2,4ꢀ;2ꢀ,4ꢀꢀ]teroxazol-2ꢀꢀ-ylmethylammonium
chloride (70)
Hydrogen chloride (4.0 M solution in dioxane) (3 mL) was added
to the carbamate 65 (0.23 g, 0.3 mmol) and the mixture was stirred
at room temperature overnight under a nitrogen atmosphere.
The mixture was evaporated to leave the a◦mine hydrochloride salt
(0.16 g, 91%) as a colourless solid; mp 191 C (decomp.); [a]2D6 +80
(c = 0.2, CH2Cl2–MeOH (3 : 1)); mmax(solid)/cm−1 3350, 1727, 1659
and 1581; dH(500 MHz, DMSO-d6) 10.33 (1H, br s, CSNH), 9.18
(1H, s, oxazole-H), 9.15 (1H, s, oxazole-H), 8.94 (1H, s, oxazole-
H), 8.92 (3H, br s, NH3), 7.99–7.95 (2H, m, 2 × phenyloxazole-H),
7.58–7.52 (3H, m, 3 × phenyloxazole-H), 5.97 (1H, br s, OH), 5.59
(1H, t, J 5.9 Hz, CSNHCH), 4.41 (2H, s, NH3CH2), 4.15–4.07
(2H, m, CH2OH) and 3.82 (3H, s, CO2CH3) ppm; dC(125 MHz,
DMSO-d6) 186.6 (s), 165.4 (s), 163.0 (s), 162.9 (s), 158.8 (s), 158.2
(s), 157.7 (s), 147.7 (d), 145.5 (d), 145.1 (s), 144.9 (d), 134.0 (d),
133.4 (s), 132.6 (s), 132.1 (d), 131.7 (d), 130.0 (s), 129.9 (s), 64.5
(t), 58.0 (d), 55.5 (q) and 38.9 (t) ppm; m/z (ESI) found: 537.1161,
C24H20N6O7S [M+] requires 537.1192.
◦
oxazole amide (0.45 g, 87%) as a colourless solid; mp 96–98 C
(from dichloromethane–petrol); [a]2D7 +54 (c = 1.0, CHCl3); found:
C, 56.9; H, 5.8; N, 11.1%. C35H42N6O10Si requires C, 57.2; H,
5.8; N, 11.4%; mmax(CHCl3)/cm−1 3696, 3605, 3506, 2929, 1719,
1680 and 1595; dH(360 MHz, CDCl3) 8.35 (1H, s, oxazole-H), 8.32
(1H, s, oxazole-H), 8.30 (1H, s, oxazole-H), 8.04–8.00 (2H, m,
2 × phenyloxazole-H), 7.83 (1H, d, J 8.7 Hz, CONH), 7.49–7.43
(3H, m, 3 × phenyloxazole-H), 5.59–5.52 (1H, m, CONHCH),
5.27 (1H, br s, BocNH), 4.56 (2H, d, J 5.8 Hz, BocNHCH2), 4.23
(1H, dd, J 10.1 and 4.6 Hz, CHaHbOTBS), 4.10 (1H, dd, J 10.1
and 5.2 Hz, CHaHbOTBS), 3.94 (3H, s, CO2CH3), 1.47 (9H, s,
OC(CH3)3), 0.84 (9H, s, SiC(CH3)3), 0.04 (3H, s, SiCH3(CH3))
and 0.03 (3H, s, SiCH3(CH3)) ppm; dC(90 MHz, CDCl3) 162.8 (s),
162.3 (s), 160.1 (s), 159.8 (s), 156.0 (s), 155.7 (s), 155.4 (s), 154.3
(d), 141.5 (d), 139.7 (d), 139.0 (d), 136.7 (s), 130.8 (s), 130.3 (d),
129.6 (s), 128.3 (d), 128.2 (d), 126.7 (s), 126.5 (s), 80.2 (s), 64.1
(t), 52.1 (q), 49.1 (d), 37.8 (t), 28.1 (q), 25.6 (q), 18.1 (s), −5.6 (q)
and −5.6 (q) ppm; m/z (ESI) found: 757.2639, C35H42N6O10SiNa
[(M + Na)+] requires 757.2629.
2-{(S)-1-[(2ꢀꢀ-{[(R)-1-((2S,3S)-2-tert-Butoxycarbonylamino-3-
methylpentanoylamino)-2-methylpropylamino]-methyl}-
[2,4ꢀ;2ꢀ,4ꢀꢀ]teroxazole-4-carbothioyl)-amino]-2-hydroxyethyl}-5-
phenyloxazole-4-carboxylic acid methyl ester (78a)
2-[(S)-1-{[2ꢀꢀ-(tert-Butoxycarbonylaminomethyl)-[2,4ꢀ;2ꢀ,4ꢀꢀ]tero-
xazole-4-carbothioyl]-amino}-2-(tert-butyldimethylsilanyloxy)-
ethyl]-5-phenyloxazole-4-carboxylic acid methyl ester (65)
4-Methylmorpholine (59 lL, 0.54 mmol) was added to a stirred
suspension of the carboxylic acid 77 (90 mg, 0.27 mmol)
and 1-hydroxybenzotriazole (0.11 g, 0.81 mmol) in dry
Lawesson’s reagent (0.45 g, 1.1 mmol) was added in one portion to
a stirred solution of the amide 64 (0.45 g, 0.61 mmol) in dry tetrahy-
drofuran (10 mL) at room temperature under a nitrogen atmo-
sphere. The mixture was stirred at reflux for 21 h and then cooled
to room temperature. The mixture was concentrated in vacuo
and the residue was then partitioned between dichloromethane
◦
dichloromethane (15 mL) at 0 C under a nitrogen atmosphere.
1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride
(0.10 g, 0.54 mmol) was added and the mixture was then stirred
at 0 ◦C for 15 min. A pre-cooled (0 ◦C) solution of the amine 70
(0.16 g, 0.27 mmol) and 4-methylmorpholine (59 lL, 0.54 mmol)
2008 | Org. Biomol. Chem., 2008, 6, 1994–2010
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