Ethyl 3-tert-butyl-1-methyl-1H-pyrazole-5-ylcarbamate (5).
Flow rate 0.5 mL min−1, 1 mmol, Yield: 90%, Rt = 3.96 min, M +
129.05 (CH), 130.70 (CH), 136.19 (C), 139.49 (C), 153.44 (C); IR:
m 3396.9, 3307.6 (m), 1705.7 (s), 1594.4 (s), 1531.3 (s), 1481.4 (m),
1454.9, 1422.4 (m), 1305, 1275.7 (s), 1222.2 (s), 1095.4, 1073.6 (m),
1054.3 (m), 995.5, 870.5, 776.6 (m), 742.3, 697.5 (m), 681.8 cm−1;
calculated for C14H13BrNO2 306.0130, found 306.0132.
1
H m/z = 226.3; H-NMR (400 MHz, CDCl3): d/ppm 6.33 (1H,
s), 6.04 (1H, s), 4.3 (2H, q, J = 8.0 Hz), 3.70 (3H, s), 1.33
(3H, t, J = 8.0 Hz), 1.29 (9H, s); 13C-NMR (100 MHz, CDCl3):
d/ppm 14.42 (CH3), 31.98 (CH3), 32.18 (C), 34.93 (CH3), 62.03
(CH2), 96.12 (C), 135.17(C), 153.98(C), 160.97 (C); IR: m 3275.9,
2959.2 (s), 2867.2, 1709.2 (s), 1570.7 (s), 1461.3 (m), 1361.9 (m),
1230.7 (s), 1095.9, 1061.6 (s), 990.4, 779.6 (m) cm−1; calculated for
C11H20N3O2 226.1556, found 226.1553.
N -(3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-yl)mor-
pholine-4-carboxamide (10). Flow rate 0.5 mL min−1, 1 mmol,
Yield: 76%, Rt = 3.82 min, M + H m/z = 340.2; 1H-NMR
(400 MHz, CDCl3): d/ppm 7.38 (1H, m), 7.30 (1H, d, J =
8.0 Hz), 7.10 (1H, dt, J = 8.5, 1.0 Hz), 5.86 (1H, br. s), 3.59
(4H, t, J = 4.5 Hz), 3.29 (4H, t, J = 4.5 Hz), 2.40 (3H, s);
13C-NMR (100 MHz, CDCl3): d/ppm 11.45 (CH3), 44.36 (2 ×
CH2), 66.27 (2 × CH2), 114.66 (CH, d, J = 22.5 Hz), 115.03 (C),
116.69 (C, d, J = 18.4 Hz), 125.64 (CH, d, J = 3.6 Hz),
131.74 (CH, d, J = 9.4 Hz), 134.74 (C, d, J = 3.9 Hz), 153.92
(C, d, J = 0.8 Hz), 155.07 (C), 160.79 (C, d, J = 251.7 Hz),
165.27 (C); IR: m 3286.8 (m), 2967.0, 2922.3, 2899.0, 2857.1,
2244.2, 1637.0 (s), 1572.3 (s), 1504.8 (s), 1456.3 (s), 1438.0 (s),
1390.0 (m), 1335.8, 1296.6 (m), 1251.8 (s), 1184.0 (m), 1149.3,
1115.2 (s), 1070.4 (m), 1019.5, 999.3 (m), 898.1 (s), 779.7 (s),
730.0 (s), 676.8 cm−1; calculated for C15H16ClFN3O3 340.0864,
found 340.0880. X-ray data: File reference: CCDC 675581;
Formula: C15H15Cl1F1N3O3·0.5(CH2Cl2); Unit cell parameters: a
25.8310(4), b 8.8237(2), c 19.7540(4), a 90.00, b 128.919(1), c
90.00; space group C2/c.
Allyl 3-bromophenylcarbamate (6)14. Flow rate 0.5 mL min−1,
1 mmol, Yield: 74%, Rt = 4.63 min, M + H m/z = 215.14
(carbamic acid); 1H-NMR (400 MHz, CDCl3): d/ppm 7.67 (1H,
s), 7.31–7.29 (1H, m), 7.21–7.14 (2H, m), 6.87 (1H, s), 5.99 (1H,
ddt, J = 17.2, 10.4, 5.5 Hz), 5.37 (1H, app. dq, J = 17.2, 1.5,
1.5 Hz), 5.29 (1H, app. dq, J = 10.4, 1.5, 1.5 Hz), 4.68 (1H, app.
dt, J = 5.5, 1.5, 1.5 Hz); 13C-NMR (100 MHz, CDCl3): d/ppm
66.51 (CH2), 118.92 (CH2), 122.08 (CH), 122.87 (CH), 123.14 (C),
126.86 (CH), 130.70 (CH), 132.60 (CH), 139.57 (C), 153.44 (C);
IR: m 3309.9 (m), 3083.3, 2946.5, 1706.6 (s), 1649.0, 1590.8 (s),
1530.4 (s), 1481.2 (s), 1421.0 (s), 1305.1 (m), 1275.3 (s), 1223.4 (s),
1167.8, 1095.7 w), 1073.6 (m), 1057.8 (m), 995.2 (m), 934.1,
867.9, 774.9 (m), 681.7 (m) cm−1; calculated for C10H10BrNO2Na
277.9800, found 277.9787.
Allyl 4-fluorophenylcarbamate (7). Flow rate 0.5 mL min−1,
1
1 mmol, Yield: 78%, Rt = 4.36 min, M + Na m/z = 219.1; H-
Methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-ylcar-
bamate (11). Flow rate 0.5 mL min−1, 1 mmol, Yield: 74%, Rt =
NMR (400 MHz, CDCl3): d/ppm 7.39–7.34 (2H, m), 7.04–6.98
(2H, m), 5.97 (1H, ddt, J = 17.2, 10.4, 5.5 Hz), 5.37 (1H, ap. dq,
J = 17.2, 1.5, 1.5 Hz), 5.27 (1H, ap. dq, J = 10.4, 1.5, 1.5 Hz),
4.68 (1H, ap. dt, J = 5.5, 1.5, 1.5 Hz), 13C-NMR (100 MHz,
CDCl3): d/ppm 66.33 (CH2), 115.99 (2 × CH, d, J = 22.5), 118.73
(CH2), 120.87 (2 × CH) 132.73 (CH), 134.16 (C), 153.87 (C),
159.40 (C, d, J = 241.2); IR: m 3315.0 (m), 2094.1, 1707.8 (s),
1614.2 (m), 1540.0 (s), 1512.3 (s), 1410.8(s), 1308.2 (m), 1221.0 (s),
1158.2, 1102.6, 1061.2 (s), 995.9, 935.1, 834.4 (s), 791.0, 769.1 cm−1;
calculated for C10H11FNO2 196.0774, found 196.0775.
1
4.12 min, M + H m/z = 285.2; H-NMR (400 MHz, CDCl3):
d/ppm 7.38 (1H, m), 7.29 (1H, d, J = 8.0 Hz), 7.10 (1H, d,
J = 8.5 Hz), 5.95 (1H, br. s), 3.62 (3H, br. s), 2.44 (3H, s);
13C-NMR (100 MHz, CDCl3): d/ppm 11.37 (CH3), 53.21 (CH3),
114.96 (CH, d, J = 21.6 Hz), 116.60 (C, d, J = 18.4 Hz), 126.08
(CH, d, J = 3.6 Hz), 132.28 (CH, d, J = 9.4 Hz), 135.44 (C,
d, J = 4.0 Hz), 153.89 (C, d, J = 0.8 Hz), 155.56 (C), 161.21
(C, d, J = 251.6 Hz), 165.64 (C); IR: m 3274.0 (m), 2956.4,
2250.6, 1718.2 (s), 1646.9 (m), 1612.3 (m), 1573.5 (s), 1530.2 (m),
1502.0 (m), 1457.7 (s), 1409.6 (m), 1373.8, 1343.3, 1251.8 (s),
1186.0, 1072.3 (s), 98.3, 902.0 (s), 786.9 (s), 734.8 (s) cm−1;
calculated for C12H11FN2O3 285.0442, found 285.0450.
3-(3-Bromophenyl)-1,1-diethylurea (8). Flow rate 0.5 mL
min−1, 1 mmol, Yield: 86%, Rt = 4.34 min, M + H m/z = 273.2;
1H-NMR (400 MHz, CDCl3): d/ppm 7.63 (1H, m), 7.26 (1H, m),
7.04–7.10 (2H, m), 6.57 (1H, br. s), 3.33 (4H, q, J = 7.5 Hz),
1.17 (6H, t, J = 7.5 Hz); 13C-NMR (100 MHz, CDCl3): d/ppm
13.85 (CH3), 42.32 (CH2), 118.44 (CH), 122.30 (C), 122.80 (CH),
125.54 (CH), 129.91 (CH), 140.83 (C), 154.39 (C); IR: m 3321.3(m),
2976.4 (m), 2931.1 (m), 2871.9, 2028.5, 1636.8 (s), 1595.3 (m),
1585.0 (s), 1519.4 (s), 1477.0 (s), 1452.4 (m), 1422.2 (s), 1401.6 (m),
1378.8 (m), 1364.9, 1301.4 (s), 1279.0 (s), 1241.6 (s), 1222.2 (m),
1162.6 (s), 1099.2, 1071.7 (m), 1085.0 (m), 1051.9, 993.9 (m),
977.0 (m), 936.3, 897.7 (m), 876.2 (m), 830.9, 790.2, 773.4 (s),
753.4 (m), 733.0 (m), 686.0 (m), 670.3 (m) cm−1; calculated for
C11H16BrN2O 271.0446, found 271.0439.
Acknowledgements
We gratefully acknowledge financial support from the RS Wolfson
Fellowship (to IRB and SVL), Insight Faraday and Syngenta (to
CDS), the Cambridge European Trust and the Ralph Raphael
Studentship award (to MB), GlaxoSmithKline (to NN) and the
BP Endowment (to SVL). We also thank VapourTec for their
collaboration and assistance during the course of this research.
We wish to thank J. E. Davies for determining the crystal structure
of compound 10. We thank the EPSRC for a financial contribution
towards the purchase of the diffractometer.
Benzyl 3-bromophenylcarbamate (9)14. Flow rate 0.5 mL
min−1, 1 mmol, Isolated yield following filtration through silica:
64%, Rt = 4.97 min, M + H m/z = 307.6; 1H-NMR (400 MHz,
CDCl3): d/ppm 7.67 (1H, s), 7.43–7.37 (5H, m), 7.30 (1H,
s), 7.22–7.15 (2H, m), 6.75 (1H, s), 5.22 (2H, s); 13C-NMR
(100 MHz, CDCl3): d/ppm 67.69 (CH2), 117.57 (CH), 122.03
(CH), 123.16 (C), 126.92 (CH), 128.73 (2 × CH) 128.88 (2 × CH),
References and notes
1 M. Baumann, I. R. Baxendale, S. V. Ley, N. Nikbin, C. D. Smith and
J. P. Tierney, Org. Biomol. Chem., 2008, DOI: 10.1039/b801631n (the
preceding paper in this issue).
2 For a series of comprehensive reviews, see: (a) S. V. Ley, I. R. Baxendale,
G. Brusotti, M. Caldarelli, A. Massi and M. Nesi, Farmaco, 2002, 57,
1592 | Org. Biomol. Chem., 2008, 6, 1587–1593
This journal is
The Royal Society of Chemistry 2008
©