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PAPER
Table 2 Physicochemical, Spectroscopic and Analytical Dataa of Compounds 2h–j, 3a–j,b and 4a–jc (continued)
Compound
1H and 31P NMR Data (DMSO-d6) , J (Hz)
Mp (°C)
133–135
3g
1H: 2.53 (s, 3 H, 2-CH3), 6.30 (s, 1 H, H1-Het), 6.70 (t, J = 6.8, 1 H, H6-Het), 6.95 (t, J = 6.7, 1 H,
H7-Het), 7.42 (d, J = 8.4, 1 H, H8-Het), 7.96 (d, J = 8.4, 1 H, NH), 9.19 (d, J = 6.9, 1 H, H5-Het)
31P: –3.45
3h
3i
1H: 2.10 (s, 3 H, 2-CH3), 7.43 (t, J = 7.3, 1 H, H6-Het), 7.33 (m, 3 H, H7-Het, 2 H-Ar + H7-Het), 7.71 269–270
(m, 2 H, 2H-Ar), 8.02 (m, 2 H, H8-Het, NH), 9.38 (d, J = 6.9, 1 H, H5-Het)
31P: –3.8
1H: 2.23 (br t, 2 H, CH2), 2.80 (br t, 2 H, CH2), 6.72 (s, 1 H, CH=), 7.40 (m, 5 H, Ar), 7.57 (d, J =
148–150
166–167
8.2, 1 H, NH)
31P: –5.0
3j
1H: 2.55 (br t, 2 H, CH2), 2.82 (br t, 2 H, CH2), 6.72 (s, 1 H, CH=), 7.47 (m, 5 H, Ar + NH)
31P: –4.5
4a
4b
4c
4d
4e
4f
1H: 3.84 (s, 3 H, N-CH3), 5.95 (t, J = 3.35, 1 H, H4-Het), 6.74 (br s, 1 H, NH2), 6.75 (d, J = 3.9, 1 H, 52–53 (Et2O)
H5-Het), 6.78 (s, 1 H, H3-Het), 7.34 (br s, 1 H, NH2)
1H: 1.93 (s, 3 H, 5-CH3), 2.19 (s, 3 H, 5-CH3), 2.41 (s, 3 H, Ar-CH3), 6.26 (s, 1 H, H4-Het), 6.43 (br 150–151 (50% aq
s, 1 H, NH2), 6.96 (br s, 1 H, NH2), 7.10 (d, J = 8.1 2 H, Ar), 7.30 (d, J = 8.1, 2 H, Ar)
EtOH)
1H: 1.97 (s, 3 H, 5-CH3), 2.23 (s, 3 H, 5-CH3), 6.31 (s, 1 H, H4-Het), 6.51 (br s, 1 H, NH2), 7.05 (br 153–154 (dec.)
s, 1 H, NH2), 7.23 (d, J = 8.1, 2 H, Ar), 7.69 (d, J = 8.1, 2 H, Ar) (Et2O)
1H: 6.85 (br s, 2 H, NH2), 7.09 (m, 2 H, H5,6-Het), 7.39 (d, J = 7.2, 1 H, H7-Het), 7.99 (d, J = 2.9, 1 200–201 (30% aq
H, H2-Het), 8.15 (d, J = 7.2, 1 H, H4-Het), 11.37 (br s, 1 H, NH-Het) MeOH)
1H: 3.81 (s, 3 H, N-CH3), 6.73 (br s, 1 H, NH2), 7.12 (m, 3 H, H5,6-Het + NH), 7.38 (d, J = 7.5, 1 H, 183–184 (50% aq
H7-Het), 7.95 (s, 1 H, H2-Het), 8.15 (d, J = 8.1, 1 H, H4-Het) EtOH)
1H: 2.65 (s, 3 H, 2-CH3), 3.70 (s, 3 H, N-CH3), 6.86 (br s, 2 H, NH2), 7.12 (m, 2 H, H5,6-Het), 7.39 222–223 (sub-
(d, J = 7.5, 1 H, H7-Het), 7.77 (d, J = 7.5, 1 H, H4-Het) lim.) (Me2C=O)
4g
4h
4i
1H: 2.50 (s, 3 H, 2-CH3), 6.25 (s, 1 H, H1-Het), 6.74 (m, 4 H, H6,7-Het, NH2), 7.35 (d, J = 8.2, 1 H, 178–180
H8-Het), 9.31 (d, J = 6.2, 1 H, H5-Het) (Me2C=O)
1H: 2.08 (s, 3 H, 2-CH3), 6.99 (t, J = 7.3, 1 H, H6-Het), 7.11 (s, 2 H, NH2), 7.28 (m, 3 H, H7-Het, 2 264–265 (i-
H-Ar, H7-Het), 7.69 (m, 2 H, 2H-Ar), 8.02 (d, J = 8.7, 1 Hz, H8-Het), 9.38 (d, J = 6.9, 1 H, H5-Het) PrOH)
1H: 2.56 (br t, 2 H, CH2), 2.83 (br t, 2 H, CH2), 6.68 (s, 1 H, =CH), 7.35 (m, 7 H, NH2, 5 H-Ar), 12.37 173–175 (50% aq
(br s, 1 H, OH)
EtOH)
4j
1H: 2.53 (br t, 2 H, CH2), 2.81 (br t, 2 H, CH2), 6.66 (s, 1 H, =CH), 7.36 (m, 6 H, NH2, 4 H-Ar), 12.73 186–187 (50% aq
(br s, 1 H, OH) EtOH)
a All compounds showed satisfactory elemental analyses C 0.08, H 0.08, N 0.04, P 0.1.
b IR (KBr): 1200–1210 (P=O), 1650–1660 (C=O) cm–1.
c IR (KBr): 1640–1650 (C=O), 3180 (N–H) cm–1.
Compound 3 was placed into a 50 mL flask and 10% aq EtOH (30
mL) was poured onto it. The mixture was then boiled under a reflux
condenser for 5 h. On cooling to r.t., the mixture was neutralized
with NaHCO3 to pH 6. The solid precipitate was filtered off and
washed on the filter with water (60 mL). When dried, the precipitate
obtained contained 85–97% pure compound 4 and was finally puri-
fied by recrystallization from an appropriate solvent (see Table 2).
Product 4a was extracted from the reaction mixture with CH2Cl2 (30
mL) and the solvent was removed under vacuum.
1H NMR spectra were recorded on Varian Gemini – 300 spectrom-
eter at 300 MHz using TMS as an internal standard. Solvents were
dried and purified prior to use. Compounds 2h–j were obtained in a
similar way to previously described 2a–g7 (for their characteriza-
tion data see Table 2).
Carboxamidophosphoric Acids 3a–j and Carboxamides 4 a–j;
General Procedure
To a stirred solution of substrate 1 (10 mmol) in heptane (30 mL)
was added isocyanatophosphoryl dichloride (1.6 g, 10 mmol). The
mixture was further stirred at r.t. for 40 min (until the 31P NMR sig-
nal at –14.0 ppm disappeared).7 The precipitate of compound 2 was
filtered off and washed with heptane (20 mL). Then ice water (30
mL) and acetone (1 mL) were poured onto it. After 5 h the mixture
was triturated and within 24 h the precipitate of compound 3 was fil-
tered off, washed with water (60 mL), and dried in the open air. For
subsequent preparation of amide 4, however, drying is not needed.
References
(1) Barton, D.; Ollis, W. D. Comprehensive Organic Chemistry,
Vol. 2; Pergamon Press: Oxford, 1979, Chap. 9.9.
(2) (a) Minisci, F.; Recupero, F.; Punta, C.; Gambarotti, C.;
Antonietti, F.; Fontanab, F.; Pedullic, G. F. Chem. Commun.
2002, 21, 2496. (b) Scott, M. K.; Baxter, E. W.; Bennett, D.
J.; Boyd, R. E.; Blum, P. S.; Codd, E. E.; Kukla, M. J.;
Synthesis 2003, No. 16, 2525–2529 © Thieme Stuttgart · New York