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H. Madani et al. / Tetrahedron 58 (2002) 8107–8111
for 3 h. Evaporation gave the crude acid chloride, which, in
CH2Cl2 (10 mL), was added to a suspension of L-proline
methyl ester (760 g, 4.6 mmol), Et3N (470 mg, 4.6 mmol)
and 4-dimethylaminopyridine (5 mg) in CH2Cl2 (5.0 mL).
The mixture was stirred for 18 h. The evaporation residue,
in EtOAc, was washed with water and brine and was dried.
Evaporation and chromatography (EtOAc) gave 15 (0.33 g,
56%) as white solid: mp 157–1588C; IR nmax 1730, 1570,
1338 cm21; NMR dH 2.03–2.09 (3H, m, proline b-H2 and
g-H), 2.31 (1H, m, proline g-H), 3.17 (1H, m, proline d-H),
3.27 (1H, m, proline d-H), 3.79 (3H, s, Me), 4.74 (1H, m,
proline a-H), 5.16 (2H, s, OCH2), 7.00 (1H, d, J¼2.7 Hz, Ar
6-H), 7.02 (1H, dd, J¼8.9, 2.7 Hz, Ar 4-H), 7.38 (5H, m,
Ph-H5), 8.16 (1H, d, J¼8.9 Hz, Ar 3-H); NMR dC 24.7,
29.6, 48.3, 58.4, 70.9, 113.9, 115.5, 127.0, 127.5, 128.4,
128.6, 134.9, 135.5, 137.6, 163.0, 163.2, 165.8, 172.1; MS
(EIþ) m/z 385.1432 (M) (C20H21N2O6 requires 385.1399).
80%) as a colourless oil: IR nmax (film) 2111, 1734 cm21
;
NMR dH 1.86 (2H, qn, J¼7 Hz, 3-H2), 1.99 (1H, t, J¼
2.6 Hz, 6-H), 2.26 (2H, td, J¼7.0, 2.6 Hz, 4-H2), 2.51 (2H, t,
J¼7.7 Hz, 2-H2), 5.14 (2H, s, PhCH2), 7.34–7.38 (5H, m,
Ph-H5); MS (FABþ) m/z 203.1076 (MþH) (C13H15O2
requires 203.1072).
4.1.12. Phenylmethyl 4-(1,2-dicarbaclosododeca-
boran(12)-1-yl)butanoate (20). Decaborane(14) (B10H14;
1.3 g, 10.9 mmol) was stirred with dry MeCN (17 mL) for
3.5 h. Ester 19 (2.17 g, 10.9 mmol) was added and the
mixture was boiled under reflux for 5 d. Evaporation and
chromatography (hexane/EtOAc; 3:2) gave 20 (1.19 g,
34%) as a white wax: mp IR nmax 1698, 2343 cm21
;
NMR dH 1.81 (2H, m, 3-H2), 2.20 (10H, br q, J¼ ca.
BH
150 Hz, B10H10), 2.21 (2H, m, 2-H2), 2.35 (2H, t, J¼7.0 Hz
4-H2), 3.50 (1H, br s, carborane 2-H), 5.11 (2H, s, CH2O),
7.34–7.40 (5H, m, Ph-H5); MS (EI) m/z 322.2721 (M)
11
4.1.9. 7-Hydroxy-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]-
benzodiazepine-5,11(10H,11aH)-dione (17). Compound
15 (480 mg, 1.3 mmol) was treated with H2 in the presence
of Pd/C (10%, 50 mg) in THF (5 mL) and MeOH (45 mL)
for 10 h. The mixture was filtered (Celitew). The evapo-
ration residue, in dry DMF (30 mL), was boiled under reflux
for 2 d. The evaporation residue, in EtOAc, was washed
with water and brine and was dried. Evaporation and
chromatography (EtOAc/MeOH 99:1) gave 17 (105 mg,
36%) as a white solid; mp 213–2148C; IR nmax 3400, 3196,
1659 cm21; NMR dH 1.80 (1H, m, 1-Hb), 1.88–1.96 (2H,
m, 2-H2), 2.48 (1H, m, 1-Ha), 3.43 (1H, m, 3-H), 3.56 (1H,
m, 3-H), 4.07 (1H, m, 11a-H), 6.94–6.92 (2H, m, 8,9-H2),
7.15 (1H, d, J¼2.7 Hz, Ar 6-H), 9.36 (1H, s, 7-OH), 10.21
(1H, s, NH); MS (EIþ) m/z 233.0927 (M) (C12H13N2O3
requires 234.0926).
(12C13H24 B10O2 requires 322.2707), 321.2748 (M)
(12C13H2411B910B1O2 requires 321.2743), (M) 320.2779
(12C13H2411B810B2O2 requires 320.2779), 319.2806 (M)
(12C13H2411B710B7O2 requires 320.2841), 318.2841 (M)
(12C13H2411B610B4O2 requires 318.2841).
4.1.13. 4-(1,2-Dicarbaclosododecaboran(12)-1-yl)buta-
noic acid (21). Ester 20 (110 mg, 0.34 mmol) was stirred
with HBr (30% in AcOH) (4.0 mL) in CH2Cl2 (6.0 mL) for
3 h. Evaporation (808C, 0.1 torr) gave 21 (38 mg, 91%) as
a white solid: mp 157–1598C (lit.17155–1578C); NMR
((CD3)2SO) dH 1.62 (2H, m, 3-H2), 2.20 (10H, br, B10H10),
2.21–2.30 (4H, m, 2,4-H4), 5.19 (1H, br, carborane 2-H),
12.22 (1H, br, OH).
4.1.14. 5,11-Dioxo-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]-
benzodiazepin-7-yl (1,2-dicarbaclosododecacarborane-
(12)-1-yl)butanoate (22). Compound 21 (7.0 mg,
30 mmol) was stirred with 17 (6.8 mg, 30 mmol), dicyclo-
hexylcarbodiimide (6.0 mg, 30 mmol) and 1-hydroxybenzo-
triazole (1.0 mg, 7.4 mmol) in dry DMF (3.0 mL), under N2
for 6.5 h. The evaporation residue, in EtOAc, was cooled to
08C and filtered. Evaporation and chromatography (EtOAc/
hexane 3:2) gave 22 (6.0 mg, 46%) as a white solid; mp 89–
918C; NMR dH 1.85 (2H, m, CH2CH2CH2), 1.93–1.98 (3H,
m, 2-H2þ1-Hb), 2.30–2.52 (2H, m, carborane-CH2), 2.4
(10H, br q, J¼B–H 150 Hz, B10H10), 2.53 (2H, t, J¼7.0 Hz,
CH2CO2), 2.68 (1H, m, 1-Ha), 3.49–3.57 (2H, m, 3-H and
carborane 2-H), 3.75 (1H, m, 3-H), 4.04 (1H, br d,
J¼5.9 Hz, 11a-H), 6.91 (1H, d, J¼8.4 Hz, 9-H), 7.14 (1H,
dd, J¼8.4, 2.7 Hz, 8-H), 7.63 (1H, d, J¼2.7 Hz, 6-H), 7.90
(1H, br, NH); MS (FABþ) m/z 446.3126 (MþH)
(12C18H2911B910B1N2O4 requires 446.3139), 445.3149 (MþH)
(12C18H2911B810B2N2O4 requires 445.3139), 444.3172 (MþH)
(12C18H2911B710B3N2O4 requires 444.3167), 443.3153 (MþH)
(12C18H2911B610B4N2O4 requires 443.3203).
4.1.10. 7-(2-Propynyloxy)-2,3-dihydro-1H-pyrrolo[2,1-c]-
[1,4]benzodiazepine-5,11-(10H,11aH)-dione (12). Com-
pound 17 (50 mg, 220 mmol) was stirred with NaH (60% in
oil, 5.3 mg, 220 mmol) in dry DMF (4.0 mL) under N2 at
08C for 15 min, then at 458C for 15 min. The mixture was
rapidly cooled to 08C, sodium iodide (32 mg, 220 mmol)
and 3-bromopropyne (80% in toluene, 62 mg, 520 mmol)
were added and the mixture was boiled under reflux for
18 h. The evaporation residue, in EtOAc, was washed with
sat. aq. NH4Cl, water and brine. Drying, evaporation and
preparative layer chromatography (hexane/EtOAc 7:3) gave
12 (24 mg, 41%) as a yellow solid; mp .2308C; IR nmax
(KBr) 3227 (N–H), 2116 (CuC), 1686 (CvO) cm21
;
NMR dH 1.95–1.98 (3H, m, 2-H2 and 1-Hb), 2.46 (1H, t,
J¼2.3 Hz, CuC-H), 2.68 (1H, m, 1-Ha), 3.54 (1H, m, 3-H),
3.75 (1H, m, 3-H), 4.00 (1H, br d, J¼5.9 Hz, 11a-H), 4.67
(2H, d, J¼2.3 Hz, OCH2), 6.88 (1H, d, J¼8.9 Hz, 9-H), 7.05
(1H, dd, J¼8.9, 3.1 Hz, 8-H), 7.49 (1H, d, J¼3.1 Hz, 6-H),
8.03 (1H, br, N–H); MS (EIþ) m/z 270.1007 (M)
(C15H14N2O3 requires 270.1004).
4.1.11. Phenylmethyl hex-5-ynoate (19). Hex-5-ynoic acid
18 (5.2 g, 46 mmol) was stirred with 1,8-diazabicyclo-
[4,5,6]undec-7-ene (10.2 g, 69 mmol) and bromomethyl-
benzene (21.1 g, 124 mmol) in dry MeCN (160 mL) for
24 h under Ar. Aq. HCl (2 M, 200 mL) was added and the
mixture was extracted twice with Et2O. Drying, evaporation
and chromatography (pentane/Et2O 19:1) gave 19 (7.5 g,
Acknowledgements
We thank Mr D. J. Wood and Mr R. R. Hartell for the NMR
spectra and Mr C. J. Cryer for the mass spectrum. We are
very grateful to the Royal Pharmaceutical Society of Great
Britain for a Research Studentship (to H. M.).