3622
A.V. Bogolubsky et al. / Tetrahedron 67 (2011) 3619e3623
3
(CeO) cmꢁ1
;
dH (500 MHz, DMSO-d6) 4.70 (q, 2H, JH,F¼8.4 Hz,
(C]O) cmꢁ1
; dH (500 MHz, DMSO-d6) 1.78e1.85 (m, 2H, CH2(Pyr)),
OCH2), 7.55 (t, 1H, 3JH,H¼8.1 Hz, ArH), 7.75 (d, 1H, 3JH,H¼8.1 Hz, ArH),
7.90 (d, 1H, 3JH,H¼8.1 Hz, ArH), 8.49 (s, 1H, ArH), 10.10 (s, 1H, NH); dC
1.85e1.89 (m, 1H, CH(Pyr)), 2.00e2.10 (m, 1H, CH(Pyr)), 2.55 (d, 3H,
3JH,H¼4.0 Hz, NCH3), 3.08e3.13 (m, 2H, NCH2(Pyr)), 3.45e3.48 (m,
2
3
(125 MHz, DMSO-d6) 61.1 (q, JC,F¼35 Hz), 113.0, 118.1, 124.0 (q,
1H, NCH(Pyr)), 5.90 (br s, 1H, NH), 6.97 (d, 1H, JH,H¼4.8 Hz, ArH),
1JC,F¼278 Hz), 125.0, 130.8, 140.2, 148.6, 152.2.
7.13e7.16 (m,1H, ArH), 7.43e7.46 (m,1H, ArH); dC (125 MHz, DMSO-
d6) 23.8, 27.4, 33.8, 46.3, 56.5, 120.3, 126.3, 127.0, 146.7, 157.4.
4.3.10. 3-Methoxyphenylcarbamic acid 2,2,2-trifluoroethyl ester 2j.
Colorless solid (69 g, 90%), mp 59e61 ꢀC; [Found: C, 47.97; H, 4.15; N,
5.52. C10H10F3NO3 requires C, 48.20; H, 4.04; N, 5.62%]; nmax (KBr)
3303 (NH), 2926 (CH),1750 (C]O), 1612,1555 (CarH), 1163, 1151 (CF),
4.3.17. 1-(3,4-Dichlorobenzyl)-3-ethyl-1-isopropyl-urea
3b. Colorless solid (462 mg, 80%), mp 92e94 ꢀC; [Found: C, 53.74;
H, 6.45; N, 9.53. C13H18Cl2N2O requires C, 53.99; H, 6.27; N, 9.69%];
nmax (KBr) 3356 (NH), 2970, 2932, 2871 (CH), 1624 (C]O), 766
1099, 1051 (CeO) cmꢁ1
; dH (500 MHz, DMSO-d6) 3.65 (s, 3H, OCH3),
4.75 (q, 2H, 3JH,F¼8.4 Hz, OCH2), 6.6 (d,1H, 3JH,H¼7.9 Hz, ArH), 7.00 (d,
1H, 3JH,H¼7.9 Hz, ArH), 7.10 (s,1H, ArH), 7.22 (t,1H, 3JH,H¼7.9 Hz, ArH),
10.05 (s, 1H, NH); dC (125 MHz, DMSO-d6) 55.5, 60.4 (q, 2JC,F¼35 Hz),
105.0, 108.9, 111.3, 124.1 (q, 1JC,F¼278 Hz), 130.2, 140.0, 152.1, 160.2.
(CCl) cmꢁ1
; dH (500 MHz, DMSO-d6) 0.99e1.01 (m, 9H, 3CH3), 3.06
(q, 2H, 3JH,H¼6.6 Hz, CH3CH2), 4.25e4.28 (m, 1H, (CH3)2CH), 4.35 (s,
2H, ArCH2), 6.35 (br s, 1H, NH), 7.20 (d, 1H, 3JH,H¼8.1 Hz, ArH), 7.44
(s, 1H, ArH), 7.57 (d, 1H, 3JH,H¼8.1 Hz, ArH); dC (125 MHz, DMSO-d6)
16.1, 21.2, 35.5, 43.3, 46.3, 127.4, 129.1, 130.7, 131.1, 143.3, 157.9,
208.9.
4.3.11. (2,5-Dimethyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trifluoroe
thyl ester 2k. Colorless solid, mp 100e102 ꢀC; [Found: C, 40.28; H,
4.33; N, 17.50. C8H10F3N3O2 requires C, 40.51; H, 4.25; N, 17.72%]; nmax
(KBr) 3179 (NH), 2957, 2846 (CH), 1741 (C]O), 1568 (CarH), 1178, 1163
4.3.18. 1-(3-Hydroxy-propyl)-3-phenyl-urea 3c. Colorless solid
(322 mg, 83%), mp 111e113 ꢀC; published mp 110e111 ꢀC.18
(CF), 1087 (CeO) cmꢁ1
; dH (500 MHz, DMSO-d6) 2.1 (s, 3H, CH3), 3.54
(s, 3H, CH3), 4.75 (q, 2H, 3JH,F¼8.4 Hz, OCH2), 8.70 (s,1H, ArH),10.05 (br
4.3.19. 1-Benzyl-3-ethyl-urea 3d. Colorless solid (306 mg, 86%), mp
96e98 ꢀC; published mp 97e98 ꢀC.19
2
s, 1H, NH); dC (125 MHz, DMSO-d6) 14.1, 35.4, 61.0 (q, JC,F¼35 Hz),
98.8, 124.0 (q, 1JC,F¼278 Hz), 136.5, 146.0, 152.6.
4.3.20. 4-Methanesulfonylpiperazine-1-carboxylic acid prop-2-yny-
lamide 3e. Colorless solid (378 mg, 77%), mp 89e90 ꢀC; [Found: C,
43.88; H, 6.37; N, 17.02. C9H15N3O3S requires C, 44.07; H, 6.16; N,
17.13%]; nmax (KBr) 3321 (NH), 2959, 2926, 2854 (CH), 1639 (C]
4.3.12. [1,3,4]Thiadiazol-2-yl-carbamic acid 2,2,2-trifluoroethyl ester
2l. Colorless solid (58 g, 84%), mp 217e218 ꢀC; [Found: C, 26.22; H,
1.84; N, 18.28. C5H4F3N3O2S requires C, 26.44; H, 1.77; N, 18.50%];
nmax (KBr) 3170 (NH), 2929 (CH), 1744 (C]O), 1172, 1153 (CF), 1107
O) cmꢁ1
; dH (400 MHz, DMSO-d6) 2.60 (s, 1H, CCH), 2.77 (s, 3H,
3
(CeO) cmꢁ1
;
dH (500 MHz, DMSO-d6) 4.99 (q, 2H, JH,F¼8.4 Hz,
SCH3), 3.08e3.12 (m, 4H, Sn(CH2)2), 3.49 (m, 4H, N(CH2)2), 3.80 (s,
2H, HNCH2), 7.00 (br s, 1H, NH); dC (125 MHz, DMSO-d6) 30.1, 34.5,
43.5, 45.7, 72.9, 83.0, 157.0.
OCH2), 9.20 (s, 1H, ArH), 12.8 (br s, 1H, NH); dC (125 MHz, DMSO-d6)
61.8 (q, JC,F¼35 Hz), 123.5 (q, 1JC,F¼278 Hz), 149.5, 153.5, 161.5.
2
4.3.13. Thiazol-2-yl-carbamic
acid
2,2,2-trifluoro-ethyl
ester
4.3.21. 3-Hydroxypiperidine-1-carboxylic
acid
cyclohexylamide
2m. Colorless solid (60 g, 87%), mp 172e173 ꢀC; [Found: C, 31.60; H,
3f. Colorless solid (340 mg, 75%), mp 74e76 ꢀC; [Found: C, 63.57; H,
9.94; N, 12.32. C12H22N2O2 requires C, 63.68; H, 9.80; N, 12.38%];
nmax (KBr) 3342 (OH), 3276 (NH), 2936, 2851 (CH), 1613 (C]
2.37; N, 12.26. C5H5F3N2O2S requires C, 31.86; H, 2.23; N, 12.39%];
nmax (KBr) 3225 (NH), 2925 (CH), 1727 (C]O), 1164, 1148 (CF), 1098
(CeO) cmꢁ1
;
dH (500 MHz, DMSO-d6) 4.90 (q, 2H, JH,F¼8.4 Hz,
O) cmꢁ1
; dH (400 MHz, DMSO-d6) 1.02e1.38 (m, 7H, CalkH),
3
3
3
OCH2), 7.25 (d, 1H, JH,H¼2.3 Hz, ArH), 7.41 (d, 1H, JH,H¼2.3 Hz,
ArH), 12.10 (br s, 1H, NH); dC (125 MHz, DMSO-d6) 61.3 (q,
2JC,F¼35 Hz), 114.2, 124.1 (q, 1JC,F¼278 Hz), 138.1, 153.2, 160.2.
1.52e1.75 (m, 7H, CalkH), 2.48e2.51 (m, 1H, CalkH), 2.30e2.33 (m,
1H, CalkH), 3.43e3.46 (m, 2H, NCH2), 3.58e3.61 (m, 1H, CalkH),
3.68e3.73 (m, 1H, CalkH), 4.51 (d, 1H, 3JH,H¼4.6 Hz, OH), 5.75 (d, 1H,
3JH,H¼5.1 Hz, NH); dC (125 MHz, DMSO-d6) 23.6, 25.6, 25.9, 33.6,
33.9, 44.0, 49.6, 51.4, 65.8, 157.2.
4.3.14. (2-Morpholin-4-yl-ethyl)-carbamic acid 2,2,2-trifluoroethyl
ester 2n. Colorless solid (64 g, 81%), mp 42e44 ꢀC; [Found: C, 41.99;
H, 6.03; N, 10.70. C9H15F3N2O3: C, 42.19; H, 5.90; N, 10.93%]; nmax
(KBr) 3200 (NH), 2972, 2951 (CH), 1730 (C]O), 1162, 1143 (CF), 1116
4.3.22. 1-(4-Chlorophenyl)-3-(1-methylpiperidin-4-yl)-urea
3g. Colorless solid (460 mg, 86%), mp 154e155 ꢀC; [Found: C,
58.23; H, 6.90; N, 15.64. C13H18ClN3O requires C, 58.31; H, 6.78; N,
15.69]; nmax (KBr) 3298 (NH), 2937 (CH), 1627 (C]O), 1587, 1571
(CeO) cmꢁ1
; dH (500 MHz, DMSO-d6) 2.26e2.44 (m, 6H, N(CH2)3),
3.15 (q, 2H, 3JH,H¼6.4 Hz, HNCH2), 3.50e3.61 (m, 4H, O(CH2)2), 4.55
3
(q, 2H, JH,F¼8.4 Hz, CF3CH2), 7.55 (br s, 1H, NH); dC (125 MHz,
(CarH) cmꢁ1
; dH (500 MHz, DMSO-d6) 1.43e1.47 (m, 2H, CalkH),
2
DMSO-d6) 38.2, 53.7, 57.8, 60.1 (q, JC,F¼35 Hz), 66.6, 124.2 (q,
2.77e2.82 (m, 2H, CalkH), 1.99e2.02 (m, 2H, CalkH), 2.18 (s, 3H,
NCH3), 2.64e2.68 (m, 2H, CalkH), 4.46e4.49 (m, 1H, HNCH), 6.00 (d,
1JC,F¼278 Hz), 154.8.
3
3
1H, JH,H¼4.9 Hz), 7.15 (d, 2H, JH,H¼7.9 Hz, ArH), 7.45 (d, 2H,
3JH,H¼7.9 Hz, ArH), 8.26 (s, 1H, ArNH); dC (125 MHz, DMSO-d6) 32.6,
46.5, 54.4, 119.5, 124.9, 128.9, 140.0, 154.8.
4.3.15. General procedure for the preparation of unsymmetrical
ureas. To a solution of 2 mmol of a trifluoroethyl carbamate and
2 mmol of an amine in 2 mL of acetonitrile, 0.2 mmol of DBU (in
case of aliphatic trifluoroethyl carbamates) was added. The reaction
mixture was heated in a pressure tube at 100 ꢀC for 4 h. Then
0.5e2 mL of water was added to the hot reaction mixture. The
product precipitated from the solution upon cooling to room
temperature. The precipitate was filtered, washed with a 1:1 water/
2-propanol solution (1e2 mL), and dried under ambient conditions.
4.3.23. 1-Ethyl-3-pyridin-3-yl-urea 3h. Colorless solid (250 mg,
76%), mp 123e125 ꢀC; published mp 123e124 ꢀC.20
4.3.24. 1-Furan-2-ylmethyl-3-(3-nitrophenyl)-urea
3i. Colorless
solid (423 mg, 81%), mp 131e133 ꢀC; [Found: C, 54.96; H, 4.41; N,
16.01. C12H11N3O4 requires C, 55.17; H, 4.24; N, 16.09%]; nmax (KBr)
3317 (NH), 2922 (CH), 1638 (C]O), 1593, 1569 (CarH), 1540 (NO2),
4.3.16. 3-Thiophen-3-yl-pyrrolidine-1-carboxylic acid methylamide
3a. Colorless solid (357 mg, 85%), mp 142e143 ꢀC; [Found: C,
56.92; H, 6.84; N, 13.16. C10H14N2OS requires C, 57.11; H, 6.71; N,
13.32]; nmax (KBr) 3358 (NH), 3108, 2971, 2937, 2875 (CH), 1618
1242 (CeO) cmꢁ1
; dH (500 MHz, DMSO-d6) 4.32 (d, 2H,
3JH,H¼5.0 Hz, HNCH2), 6.26e6.28 (m, 1H, ArH), 6.40e6.42 (m, 1H,
ArH), 6.75 (br s, 1H, CH2NH), 7.52 (t, 1H, 3JH,H¼8.1 Hz, ArH), 7.60 (s,
3
3
1H, ArH), 7.67 (d, 1H, JH,H¼8.1 Hz, ArH), 7.77 (d, 1H, JH,H¼8.1 Hz,