F
C. Steinebach et al.
PSP
Synthesis
tert-Butyl N-{(1S)-1-[(2S,4R)-2-({2-[tert-butyl(diphenyl)silyl]oxy-
4-(4-methylthiazol-5-yl)phenyl}methylcarbamoyl)-4-hydroxy-
pyrrolidine-1-carbonyl]-2,2-dimethylpropyl}carbamate (9)
Funding Information
I.S. acknowledges funding by the Javna Agencija za Raziskovalno De-
javnost RS [Slovenian Research Agency (ARRS)] through research core
This compound was prepared using General Procedure IV, compound
8d (1.34 g, 2.0 mmol), and Boc-Tle-OH (0.46 g, 2.0 mmol). The crude
product was purified by flash chromatography on silica gel (0% to 5%
MeOH in CH2Cl2) to yield the title compound as a colorless solid;
yield: 0.94 g (60%); mp 108–110 °C; Rf = 0.43 (CH2Cl2/MeOH 9:1).
funding No. P1-0208.
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Acknowledgment
1H NMR (600 MHz, DMSO-d6): = 0.94 [s, 9 H, C(CH3)3], 1.06 [s, 9 H,
SiC(CH3)3], 1.39 [s, 9 H, OC(CH3)3], 1.84 (s, 3 H, CH3), 1.94–2.01 (m, 1
H), 2.05–2.12 (m, 1 H, 3-H), 3.59–3.72 (m, 2 H, 5-H), 4.13–4.20 (m, 1
H), 4.36–4.46 (m, 2 H), 4.50–4.59 (m, 2 H, 2-H, 4-H, NHCH, NHCH2),
5.15 (d, J = 2.5 Hz, 1 H, OH), 6.37 (d, J = 1.3 Hz, 1 H), 6.88 (dd, J = 1.7,
7.9 Hz, 1 H), 7.43–7.52 (m, 8 H), 7.69–7.73 (m, 4 H, ArH, CONH), 8.54
(t, J = 6.3 Hz, 1 H, CONH), 8.80 (s, 1 H, 2′′-H).
13C NMR (151 MHz, DMSO-d6): = 15.35 (CH3), 18.96 [SiC(CH3)3],
26.25 [SiC(CH3)3, CHC(CH3)3], 28.18 [OC(CH3)3], 35.36 [CHC(CH3)3],
37.60 (C-3), 38.22 (NHCH2), 56.36, 58.42, 58.83 (C-2, C-5, NHCH),
69.92 (C-4), 78.08 [OC(CH3)3], 117.76 (C-3′), 121.43 (C-5′′), 128.21,
128.77, 130.01, 130.39, 131.44, 134.94 (C-Ar), 147.30 (C-4′′), 151.38
(C-2′′), 152.18 (C-2′), 155.35, 169.93, 172.17 (C=O).
G. S. thanks Prof. A. C. Filippou for support. The authors thank Hannes
Buthmann, Deborah Schlipphack, Nicole Schmitt, and Eva Wiemann
for synthetic support.
Supporting Information
Supporting information for this article is available online at
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References
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LC-MS (ESI) (90% H2O to 100% MeOH in 10 min, then 100% MeOH to
20 min, DAD 200–350 nm): tR = 12.82 min, 95% purity; m/z [M +
H]+calcd for C43H57N4O6SSi: 785.38; found: 785.5.
HRMS (ESI): m/z [M + H]+ calcd for C43H57N4O6SSi: 785.3763; found:
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785.3739.
(2S,4R)-N-({2-[tert-Butyl(diphenyl)silyl]oxy-4-(4-methylthiazol-
5-yl)phenyl}methyl)-1-{(2S)-2-[(1-cyanocyclopropanecarbonyl)-
amino]-3,3-dimethylbutanoyl}-4-hydroxypyrrolidine-2-carbox-
amide (10)
This compound was prepared using General Procedure IV, compound
9 (0.79 g, 1.0 mmol), and 1-cyano-1-cyclopropanecarboxylic acid
(0.11 g, 1.0 mmol). The crude product was purified by flash chroma-
tography on silica gel (0% to 5% MeOH in CH2Cl2) to afford the title
compound as a slight yellow solid; yield: 0.60 g (77%); mp 112–
114 °C; Rf = 0.37 (CH2Cl2/MeOH 9:1).
1H NMR (600 MHz, DMSO-d6): = 0.97 [s, 9 H, C(CH3)3], 1.07 [s, 9 H,
SiC(CH3)3], 1.45–1.56 (m, 2 H), 1.58–1.66 (m, 2 H, 2′′′-H), 1.84 (s, 3 H,
CH3), 1.94–2.00 (m, 1 H), 2.09–2.15 (m, 1 H, 3-H), 3.59 (d, J = 11.0 Hz,
1 H), 3.64–3.68 (m, 1 H, 5-H), 4.27–4.40 (m, 1 H), 4.42–4.61 (m, 4 H,
2-H, 4-H, NHCH, NHCH2), 5.17 (d, J = 3.7 Hz, 1 H, OH), 6.38 (d, J = 1.7
Hz, 1 H), 6.90 (dd, J = 1.7, 7.9 Hz, 1 H), 7.37–7.53 (m, 8 H), 7.69–7.73
(m, 4 H, ArH, CONH), 8.59 (t, J = 5.9 Hz, 1 H, CONH), 8.80 (s, 1 H, 2′′-H).
13C NMR (151 MHz, DMSO-d6): = 13.72 (C-1′′′), 15.33 (CH3), 16.58,
16.77 (C-2′′′), 18.96 [C(CH3)3], 26.05 [C(CH3)3], 26.24 [C(CH3)3], 36.21
[C(CH3)3], 37.60 (C-3), 37.90 (NHCH2), 56.65, 57.36, 58.87 (C-2, C-5,
NHCH), 69.89 (C-4), 117.86 (C-3′), 120.10 (CN), 121.43 (C-5′′), 128.22,
128.65, 130.12, 130.38, 130.52, 131.39, 134.94 (C-Ar, C-1′, C-4′, C-5′,
C-6′), 147.33 (C-4′′), 151.40 (C-2′′), 152.24 (C-2′), 164.42, 168.75,
171.87 (C=O).
LC-MS (ESI) (90% H2O to 100% MeOH in 10 min, then 100% MeOH to
20 min, DAD 200–330 nm): tR = 12.51 min, 100% purity; m/z [M +
H]+calcd for C43H52N5O5SSi: 779.05; found: 778.7.
HRMS (ESI): m/z [M + H]+ calcd for C43H52N5O5SSi: 778.3453; found:
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G