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Concise Article
6-((tert-butoxycarbonyl)amino)hexanoic acid (129 mg, 560 mmol) min, 98% purity. HRMS (m/z): [MH]+ calcd for C44H50N4O6,
was added to the brown solution, and the reaction mixture was 731.3803; found 731.3836.
allowed to stir at rt for 2 days. Solvent was removed in vacuo, then
N1,N6-Bis(3-(6aR)-(apomorphin-O10-yl)propyl)adipamide
the mixture was taken up in EtOAc (20 mL) and washed with
saturated NaHCO3 solution (2 ꢂ 20 mL), brine (20 mL), then
ditriuoroacetate (7b)
dried over anhydrous Na2SO4 and evaporated to dryness to give
Hexanedioic acid used as carboxylic acid. Isolated as a white
the crude product as a brown oil (157 mg, 58%). The product was
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amorphous solid (21 mg, 15%). H NMR (400 MHz, CD3CN) d
then puried by preparatory HPLC to give the title compound as
8.28 (d, J ¼ 7.8 Hz, 2H), 7.33 (t, J ¼ 7.7 Hz, 2H), 7.11 (d, J ¼ 7.6
a white amorphous solid as the TFA salt, then washed with
Hz, 2H), 6.82 (d, J ¼ 8.1 Hz, 2H), 6.75–6.60 (m, 4H), 4.11–3.94
NH4OH solution (5 mL) and extracted with DCM to give the title
(m, 6H), 3.64 (dd, J ¼ 11.7, 5.3 Hz, 2H), 3.48–3.13 (m, 10H), 3.05–
2.87 (m, 8H), 2.82 (t, J ¼ 13.7 Hz, 2H), 2.15–2.07 (m, 4H), 1.93–
1.84 (m, 4H), 1.56–1.48 (m, 4H). 13C NMR (101 MHz, CD3CN) d
174.3 (C), 161.3 (q, 2JCF ¼ 35.5 Hz, C), 147.0 (C), 145.2 (C), 133.0
(C), 131.0 (C), 129.4 (C), 128.9 (CH), 128.3 (CH), 128.2 (CH),
compound as a pale green oil. 1H NMR (400 MHz, CD3OD) d 8.46
(d, J ¼ 7.9 Hz, 1H), 8.07 (t, J ¼ 5.7 Hz, 1H), 7.39 (t, J ¼ 7.7 Hz, 1H),
7.19 (d, J ¼ 7.7 Hz, 1H), 6.91 (d, J ¼ 8.2 Hz, 1H), 6.83 (d, J ¼ 8.1 Hz,
1H), 4.33 (d, J ¼ 13.1 Hz, 1H), 4.16–4.05 (m, 2H), 3.81 (dd, J ¼ 12.0,
5.2 Hz, 1H), 3.63–3.49 (m, 1H), 3.60–3.34 (m, 5H), 3.24–3.08 (m,
4H), 2.97 (t, J ¼ 7.0 Hz, 2H), 2.80 (t, J ¼ 14.0 Hz, 1H), 2.20 (t, J ¼ 7.5
Hz, 2H), 2.02 (p, J ¼ 6.5 Hz, 2H), 1.66–1.54 (m, 2H), 1.50–1.39 (m,
9H), 1.36–1.24 (m, 2H). 13C NMR (101 MHz, CD3OD) d 176.4 (C),
156.1 (C), 148.0 (C), 145.8 (C), 133.8 (C), 130.4 (C), 129.3 (CH),
129.0 (CH), 128.4 (CH), 126.8 (C), 120.8 (C), 119.9 (CH), 112.9
(CH), 79.0 (C) 67.8 (CH2), 56.4 (CH2), 53.5 (CH2), 49.9 (CH3), 43.6
(CH), 42.1 (CH2), 41.2 (CH2), 37.5 (CH2), 37.1 (CH2), 34.7 (CH2),
32.7 (CH2), 30.7 (CH2), 30.1 (CH2), 28.8 (CH3), 27.4 (CH2), 26.7
(CH2), 25.7 (CH2). HPLC (l ¼ 254 nm) tR ¼ 9.34 min, 98% purity.
HRMS (m/z): [M ꢃ H]ꢃ calcd for C31H43N3O5, 536.3130; found
536.3117.
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127.3 (C), 120.4 (C), 120.0 (CH), 117.5 (q, JCF ¼ 292.5 Hz, C),
113.4 (CH), 67.2 (CH2), 63.1 (CH), 53.1 (CH2), 42.4 (CH3), 36.5
(CH2), 36.2 (CH2), 32.0 (CH2), 29.7 (CH2), 26.6 (CH2), 25.9 (CH2).
HPLC tR ¼ 7.96 min, >99% purity. HRMS (m/z): [MH]+ calcd for
C
46H54N4O6, 759.4116; found 759.4120.
Acknowledgements
J. S. acknowledges an Australian Postgraduate Award. J. R. L. is a
Monash University Larkins Fellow and a R D Wright Biomedical
Career Development Fellow (NHMRC). This work was funded in
part by NHMRC Program Grant No. APP1011920.
Notes and references
General procedure for the preparation of bivalent ligands
4 (2.2 equiv.) was taken up in DCM (3 mL) and to the brown
solution at rt was added N,N-diisopropylethylamine (2.2 equiv.),
octanedioic acid (1 equiv.) and (benzotriazol-1-yloxy)tris(dime-
thylamino)phosphonium hexauorophosphate (2.2 equiv.)
under a nitrogen atmosphere. Aer stirring for 2 h, the mixture
was evaporated to dryness and the product puried by
ash column chromatography (CHCl3–CH3OH, 10 : 1 + 0.1%
NH4OH) to give a brown oil, then further puried by preparatory
HPLC (100–30% solvent A [99.9% water, 0.01% triuoroacetic
acid] in solvent B [80% CH3CN, 19.9% water, 0.01% triuoro-
acetic acid]) to give the title compound as a white amorphous
solid as the di-TFA salt.
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¨
¨
¨
¨
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2
(C), 161.2 (q, JCF ¼ 35.1 Hz, C), 145.7 (C), 143.9 (C), 131.7 (C),
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1
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