2270
A. Kaiser, C. Richert
LETTER
g, 15.6 mmol, 72%). Yellowish powder, mp 35 °C. IR
(neat): 3119, 2962, 2559, 2369, 2105, 1967, 1766, 1617,
1594, 1523, 1491, 1347, 1198 cm–1. 1H NMR (300 MHz,
CDCl3): d = 5.32 (s, 2 H, CH2N3), 7.40–7.46 (m, 2 H, ArH),
8.28–8.34 (m, 2 H, ArH). 13C NMR (75 MHz, CDCl3):
d = 78.96 (CH2), 121.74 (CH), 125.45 (CH), 145.72, 152.29,
155.04. MS (EI, 70 eV): m/z (%) = 238 (2) [M]+, 196 (12),
166 (36), 139 (40), 122 (42), 56 (100), 28 (71). HRMS (EI):
m/z calcd for C8H6N4O5: 238.0338 [M]+; found: 238.0319
[M]+. Anal. Calcd for C8H6N4O5: C, 40.35; H, 2.54; N,
23.53. Found: C, 40.25; H, 2.69; N, 23.26.
chromatography using a gradient of CH2Cl2 → CH2Cl2–
MeOH (99:1).
Orange brownish powder; mp 136–138 °C. IR (neat): 3509,
3310, 2958, 2163, 2141, 2112, 1967, 1717, 1679, 1586, 1565
cm–1. 1H NMR (500 MHz, DMSO-d6): d = 3.72 (s, 3 H, Me),
3.82 (s, 3 H, Me), 5.27 (s, 2 H, CH2N3), 6.69 (d, 4J = 1.9 Hz,
1 H, ArH), 7.14 (d, 4J = 1.9 Hz, 1 H, ArH), 9.80 (s, 1 H, NH).
13C NMR (126 MHz, DMSO-d6): d = 36.09, 50.88, 74.88,
107.56, 118.99, 119.47, 121.92, 152.38, 160.54. ESI-
HRMS: m/z calcd for C9H11N5O4Na: 276.0703 [M + Na]+;
found: 276.0716 [M + Na]+.
(11) General Procedure for Azoc Protection with
Azidomethyl 4-Nitrophenyl Carbonate (1) and
(12) Baird, E.; Dervan, P. B. J. Am. Chem. Soc. 1996, 118, 6141.
(13) Ammonium 2-[(Azidomethoxy)carbonylamino]ethyl
Hydrogenphosphate (6h)
Analytical Data of Compounds 6b,d,g
Azidomethyl 4-nitrophenyl carbonate (1, 300 mg, 1.26
mmol, 1.0 equiv) was dissolved in anhyd DMF (3 mL) and
cooled to 0 °C. Either of compounds 5a–g (1.26 mmol) was
dissolved in anhyd DMF (2 mL) in an separate flask and
treated with DIPEA (1.39 mmol, 236 mL, 1.1 equiv). The
resulting solution was added dropwise, within 2 min, to the
solution of 1. The reaction was monitored via TLC (CH2Cl2–
PE = 3:2). After complete conversion, the reaction mixture
was diluted with EtOAc (200 mL) and washed with Na2CO3
solution (8 × 50 mL, 2 M). The combined aqueous solutions
were re-extracted with EtOAc (30 mL). The extract was
washed once with H2O (10 mL). The combined organic
phases were washed with sat. NaCl solution (2 × 50 mL),
dried over Na2SO4, filtered, concentrated in vacuo and dried
at <10–3 mbar for at least 3 h. Analytical data of compounds
6a and 6f were found to be identical to those in ref. 2.
Azidomethyl 4-Aminobenzylcarbamate (6b)
Azidomethyl 4-nitrophenyl carbonate (1, 300 mg, 1.26
mmol, 1.0 equiv) and 2-aminoethyl dihydrogen phosphate
(177.7 mg, 1.26 mmol, 1.0 equiv) were added to a flask and
suspended in DMF (4 mL). DIPEA (4.16 mmol, 707 mL, 3.3
equiv) and H2O (3 mL) were added. The resulted suspension
was sonicated for 2 min and then stirred at 20 °C. After 20
min, a clear solution formed. A complete conversion was
detected after 30 min via TLC (CH2Cl2–PE = 3:2). The
reaction mixture was diluted with H2O (200 mL) and poured
on a DEAE-cellulose column [100 g, 20 cm, HCO3– form,
Express-Ion exchanger D, Whatman (Maidstone, UK)]. The
column was washed with H2O (200 mL) and 100 mM
NH4HCO3 solution (500 mL). The product-containing
fractions were combined and the resulting solution
concentrated to 20 mL, followed by lyophilization to
dryness. The title compound 6h was obtained as a colorless
solid (321 mg, 1.25 mmol, 99%). IR (neat): 3210, 2889,
2103, 1705, 1532, 1455 cm–1. 1H NMR (300 MHz, D2O):
d = 3.28 (t, 3J = 5.3 Hz, 2 H), 3.75–3.83 (m, 2 H), 5.06 (s,
2 H, CH2N3). 13C NMR (75 MHz, D2O): d = 41.25 (d,
3JP–C2 = 7.8 Hz, C-2), 63.59 (d, 2JP–C1 = 5.2 Hz, C-1), 75.71
(CH2N3), 157.35 (C=O). 31P NMR (121.5 MHz, D2O):
d = 1.10. ESI-HRMS: m/z calcd for C4H8N4O6P: 239.0187
[M]–; found: 239.0175 [M]–.
Orange oil which slowly crystallized at –18 °C (2 weeks) to
give an orange solid with mp 26–28 °C. IR (neat): 3423,
3328, 2154, 2098, 1723, 1697, 1617, 1539, 1512 cm–1. 1H
NMR (300 MHz, CDCl3): d = 3.68 (s, 2 H, NH2), 4.27 (d,
3J = 5.9 Hz, 2 H, CH2Ar), 5.05–5.20 (m, 3 H, CH2N3, NH),
6.62–6.68 (m, 2 H, ArH), 7.08 (d, 3J = 8.3 Hz, 2 H, ArH). 13
C
NMR (75 MHz, CDCl3): d = 44.89 (ArCH2), 75.32 (CH2N3),
115.25, 127.59, 128.72, 129.04, 146.08, 155.18. ESI-
HRMS: m/z calcd for C9H11N5O2Na: 244.0805 [M + Na]+;
found: 244.0802 [M + Na]+.
(14) Ammonium 3-[(Azidomethoxy)carbonylamino]-
propanoate (6i)
A sample of b-alanine (112.2 mg, 1.26 mmol) was treated as
described in ref. 13 but in the presence of a smaller amount
of DIPEA (471 mL, 2.77 mmol, 2.2 equiv). The column
purification used a higher concentration of NH4HCO3 (250
mM) for elution from the DEAE-cellulose. The title
compound was obtained as colorless oil (236.2 mg, 1.15
mmol, 91%). IR (neat): 3231, 2965, 2103, 1967, 1701, 1524,
1447, 1409, 1219 cm–1. 1H NMR (300 MHz, D2O): d = 2.44
(t, 3J = 6.6 Hz, 2 H), 3.31 (t, 3J = 6.6 Hz, 2 H), 5.06 (s, 2 H,
CH2N3). 13C NMR (75 MHz, D2O): d = 34.95, 36.79, 75.62
(CH2N3), 157.14, 177.60. ESI-HRMS: m/z calcd for
C5H7N4O4: 187.0473 [M]–; found: 187.0468 [M]–.
(15) Bentley, D. R. et al. Nature (London) 2008, 456, 53.
Azidomethyl 5-Hydroxypentylcarbamate (6d)
Colorless oil. IR (neat): 3329, 2937, 2864, 2140, 2100, 1705,
1532 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.36–1.48 (m,
2 H, H-3), 1.51–1.65 (m, 5 H, H-2, H-4, OH), 3.24 (q,
3J = 6.7 Hz, 2 H, CH2NH), 3.65 (t, 3J = 6.4 Hz, 2 H,
CH2OH), 5.02 (s, 1 H, NH), 5.13 (s, 2 H, CH2N3). 13C NMR
(75 MHz, CDCl3): d = 22.87 (C-3), 29.51, 32.13, 41.02 (C-
1), 62.55 (C-5), 75.22 (CH2N3), 155.36 (C=O). ESI-HRMS:
m/z calcd for C7H14N4O3Na: 225.0958 [M + Na]+; found:
225.0964 [M + Na]+.
Methyl 4-[(Azidomethoxy)carbonylamino]-N-methyl-
pyrrole-2-carboxylate (6g)
Compound 6g was purified via flash column
Synlett 2010, No. 15, 2267–2270 © Thieme Stuttgart · New York