Passerini Reactions with vic-Diketo Amides
on a 0.54 mmol scale using 7b, after a reaction time of 24 h, and
using tert-butyl methyl ether as eluent, 26a (219 mg, 0.50 mmol,
92%) was isolated as a colourless solid. TLC (tert-butyl methyl
2-(Morpholinocarbonyl)-1-(naphthalen-2-ylamino)-1,3-dioxobutan-
2-yl Acetate (26d): Following general procedure C in dichlorometh-
ane on a 0.54 mmol scale using 7b, after a reaction time of 21.5 h,
ether): Rf = 0.18; m.p. 75 °C (chloroform). 1H NMR (400 MHz, and using diethyl ether as eluent, 26d (209 mg, 0.52 mmol, 97%)
CDCl3): δ = 8.58 (br. s, 1 H, NH), 7.73 (d, J = 8.3 Hz, 2 H, 2
Hortho), 7.35 (d, J = 8.2 Hz, 2 H, 2 Hmeta), 4.75 (dd, J = 14.1, J = m.p. 74 °C (chloroform). H NMR (500 MHz, CDCl3): δ = 10.14
was isolated as a pale yellow solid. TLC (diethyl ether): Rf = 0.31;
1
7.0 Hz, 1 H, NHCH2), 4.62 (dd, J = 14.1, J = 6.6 Hz, 1 H,
NHCH2), 3.82–3.39 [m, 8 H, N(C2H4)2O], 2.44 (s, 3 H, CH3Ar),
(s, 1 H, NH), 8.21 (d, J = 2.0 Hz, 1 H, 1Ј-H), 7.82–7.76 (m, 3 H,
4Ј-H, 5Ј-H, 8Ј-H), 7.49 (dd, J = 8.8, J = 2.2 Hz, 1 H, 3Ј-H), 7.46
2.24 (s, 3 H, CH3CO2), 2.19 (s, 3 H, 4-H3) ppm. 13C NMR (ddd, J = 7.8, J = 7.1, J = 1.5 Hz, 1 H, 7Ј-H), 7.42 (ddd, J = 7.9,
(75 MHz, CDCl3): δ = 197.1 (C-3), 168.6 (CO2), 163.1 (C-1), 162.3
J = 7.0, J = 1.6 Hz, 1 H, 6Ј-H), 3.99–3.49 [m, 8 H, N(C2H4)2O],
[2-CON(C2H4)2O], 145.5 (Cipso), 134.3 (Cpara), 130.2 (2 C, 2 Cmeta), 2.37 (s, 3 H, 4-H3), 2.34 (s, 3 H, CH3CO2) ppm. 13C NMR
128.9 (2 C, 2 Cortho), 87.3 (C-2), 66.5 (2 C, 2 OCH2), 60.6 (NHCH2), (75 MHz, CDCl3): δ = 198.0 (C-3), 168.9 (CH3CO2), 163.1 [2-
47.1 (NCH2), 44.2 (NCH2), 25.5 (C-4), 21.8 (CH3Ar), 20.6
CON(C2H4)2O], 160.5 (C-1), 134.6 (C-2Ј), 133.9 (C-8aЈ), 131.2 (C-
(CH CO ) ppm. FTIR (neat): ν = 3336 (w), 3935 (w), 3858 (w), 4aЈ), 129.0, 127.9, 127.7, 126.8 (C-7Ј), 125.5 (C-6Ј), 120.3 (C-3Ј),
˜
3
2
2120 (w), 1759 (m), 1733 (m), 1699 (s), 1643 (s), 1598 (w), 1516 (m),
117.5 (C-1Ј), 87.5 (C-2), 66.8 (2 C, 2 OCH2), 47.2 (NCH2), 44.2
1435 (m), 1365 (w), 1321 (m), 1294 (m), 1215 (s), 1141 (s), 1113 (s), (NCH ), 25.8 (C-4), 20.7 (CH CO ) ppm. FTIR (neat): ν =
˜
2
3
2
1083 (m), 1020 (w), 975 (m), 933 (w), 886 (w), 857 (w), 817 (m),
752 (m), 668 (w), 565 (s), 511 (s), 455 (m), 411 (w) cm–1. HRMS
(ESI): calcd. for C19H24N2O8SNa [M + Na]+ 463.1146; found
463.1147.
3316 (w), 3054 (w), 2966 (w), 2922 (w), 2856 (w), 1759 (m),
1731 (m), 1694 (s), 1640 (s), 1594 (m), 1543 (s), 1502 (m), 1431 (s),
1359 (s), 1299 (w), 1216 (s), 1109 (s), 1019 (m), 973 (m), 933 (w),
888 (m), 854 (m), 813 (m), 749 (m), 703 (w), 662 (w), 594 (m),
521 (w), 474 (m), 427 (w) cm–1 . HRMS (ESI): calcd. for
C21H22N2O6Na [M + Na]+ 421.1370; found 421.1372.
Methyl 2-[2-Acetoxy-2-(morpholinocarbonyl)-3-oxobutanamido]-
acetate (26b): Following general procedure C in dichloromethane
on a 0.54 mmol scale using 7b, after a reaction time of 20 h, and
using tert-butyl methyl ether as eluent, 26b (162 mg, 0.47 mmol,
87%) was isolated as a colourless solid. TLC (ethyl acetate): Rf =
1-(4-Methoxyphenylamino)-2-(morpholinocarbonyl)-1,3-dioxobutan-
2-yl Acetate (26e): Following general procedure C in dichlorometh-
ane on a 0.54 mmol scale using 7b, after a reaction time of 21 h,
and using tert-butyl methyl ether as eluent, 26e (205 mg,
0.54 mmol, 100%) was isolated as an orange solid. TLC (tert-butyl
methyl ether): Rf = 0.29; m.p. 154 °C (chloroform). 1H NMR
(500 MHz, CDCl3): δ = 9.73 (s, 1 H, NH), 7.46–7.41 (m, 2 H, 2
Hortho), 6.88–6.84 (m, 2 H, 2 Hmeta), 3.96–3.44 [m, 8 H, N(C2H4)
2O], 3.79 (s, 3 H, OCH3), 2.33 (s, 3 H, 4-H3), 2.31 (s, 3 H, CH3CO2)
ppm. 13C NMR (125 MHz, CDCl3): δ = 198.1 (C-3), 169.0
(CH3CO2), 163.0 [2-CON(C2H4)2O], 160.1 (C-1), 157.1 (Cpara),
130.3 (Cipso), 122.1 (2 C, 2 Cortho), 114.3 (2 C, 2 Cmeta), 87.4 (C-2),
66.7 (2 C, 2 OCH2), 55.6 (OCH3), 47.2 (NCH2), 44.2 (NCH2), 25.9
1
0.51; m.p. 105 °C. H NMR (400 MHz, CDCl3): δ = 8.02 (br. s, 1
H, NH), 4.10 (dd, J = 17.9, J = 5.6 Hz, 1 H, NHCH2), 4.04
(dd, J = 18.0, J = 5.7 Hz, 1 H, NHCH2), 3.92–3.40 [m, 8 H,
N(C2H4)2O], 3.75 (s, 3 H, OCH3), 2.31 (s, 3 H, 4-H3), 2.28 (s, 3 H,
CH3CO2) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.8 (C-3),
169.2 (CO2Me), 168.8 (CH3CO2), 163.2 (C-1), 162.6 [2-
CON(C2H4)2O], 87.9 (C-2), 66.7 (2 C, 2 OCH2), 52.6 (OCH3), 47.0
(NCH2), 44.0 (NCH2), 41.8 (NHCH2), 25.9 (C-4), 20.7 (CH3CO2)
ppm. FTIR (neat): ν = 3304 (w), 2926 (w), 2863 (w), 1742 (s),
˜
1678 (m), 1645 (s), 1511 (m), 1438 (m), 1367 (m), 1304 (w),
1258 (m), 1204 (s), 1170 (s), 1108 (s), 1066 (w), 1019 (w), 978 (m),
933 (w), 892 (w), 865 (w), 804 (w), 713 (m), 687 (w), 657 (w),
588 (m), 528 (m), 467 (m) cm–1. HRMS (ESI): calcd. for
C14H20N2O8Na [M + Na]+ 367.1112; found 367.1112.
(C-4), 20.7 (CH CO ) ppm. FTIR (neat): ν = 3318 (w), 2926 (w),
˜
3
2
2855 (w), 1760 (m), 1731 (m), 1690 (s), 1643 (s), 1600 (m), 1512 (s),
1437 (m), 1363 (m), 1302 (w), 1219 (s), 1177 (s), 1108 (s), 1026 (s),
976 (m), 935 (w), 900 (w), 828 (s), 753 (m), 664 (w), 596 (m),
517 (m), 452 (m) cm–1. HRMS (ESI): calcd. for C18H23N2O7 [M +
H]+ 379.1500; found 379.1505.
1-[(Diethoxyphosphoryl)methylamino]-2-(morpholinocarbonyl)-
1,3-dioxobutan-2-yl Acetate (26c): Following general procedure C
in dichloromethane on a 0.54 mmol scale using 7b, after a reaction
time of 24 h, and using chloroform/methanol, 20:1 as eluent, 26c
(228 mg, 0.54 mmol, 100 %) was isolated as a colourless liquid.
TLC (chloroform/methanol, 20:1): Rf = 0.36. 1H NMR (300 MHz,
CDCl3): δ = 8.06 (br. s, 1 H, NH), 4.15 (ddd, J = 8.1, J = 7.0, J =
6.0 Hz, 2 H, POCH2), 4.11 (ddd, J = 8.1, J = 7.1, J = 5.9 Hz, 2 H,
POCH2), 3.79 (ddd, J = 15.8, J = 12.4, J = 6.3 Hz, 1 H, NHCH2),
3.69 (ddd, J = 15.8, J = 12.2, J = 5.8 Hz, 1 H, NHCH2), 3.71–3.44
[m, 8 H, N(C2H4)2O], 2.28 (s, 3 H, 4-H3), 2.27 (s, 3 H, CH3CO2)
1.32 [dt, J = 6.9, J = 5.8 Hz, 6 H, P(OCH2CH3)2] ppm. 13C NMR
(75 MHz, CDCl3): δ = 196.9 (C-3), 168.7 (CH3CO2), 162.8 (d, J =
5.9 Hz, C-1), 162.8 [2-CON(C2H4)2O], 87.6 (C-2), 66.6 (2 C, 2
OCH2), 62.8 [d, J = 6.5 Hz, 2 C, P(OCH2)2], 47.0 (NCH2), 44.0
(NCH2), 35.7 (d, J = 156.8 Hz, NHCH2), 25.7 (C-4), 20.7
(CH3CO2), 16.5 (d, J = 5.1 Hz, POCH2CH3), 16.5 (d, J = 5.0 Hz,
POCH2CH3) ppm. 31P NMR (202 MHz, CDCl3): δ = 21.5 ppm.
2-(Morpholinocarbonyl)-1,3-dioxo-1-(3-oxobutylamino)butan-2-yl
Acetate (26f): Following general procedure C in dichloromethane
on a 0.62 mmol scale using 7b, after a reaction time of 16 h, and
using ethyl acetate as eluent, 26f (210 mg, 0.61 mmol, 99%) was
1
isolated as a colourless liquid. TLC (ethyl acetate): Rf = 0.29. H
NMR (400 MHz, CDCl3): δ = 7.82 (br. s, 1 H, NH), 3.78–3.45 [m,
10 H, N(C2H4)2O, 1Ј-H2], 2.69 (dt, J = 6.2, J = 3.2 Hz, 2 H, 2Ј-
H2), 2.27 (s, 3 H, 4-H3), 2.26 (s, 3 H, CH3CO2), 2.15 (s, 3 H, 4Ј-
H3) ppm. 13C NMR (75 MHz, CDCl3): δ = 207.0 (C-3Ј), 197.2 (C-
3), 168.8 (CH3CO2), 162.9 [2-CON(C2H4)2O], 162.8 (C-1), 87.8 (C-
2), 66.7 (2 C, 2 OCH2), 46.9 (NCH2), 44.0 (NCH2), 42.6 (C-2Ј),
35.2 (C-1Ј), 30.2 (C-4Ј), 25.9 (C-4), 20.8 (CH3CO2) ppm. FTIR
(neat): ν = 3599 (w), 3348 (w), 2926 (w), 2860 (w), 1761 (m),
˜
1683 (s), 1644 (s), 1522 (m), 1433 (m), 1363 (m), 1302 (w), 1215 (s),
1174 (s), 1111 (s), 1020 (m), 976 (m), 932 (w), 891 (w), 858 (w),
833 (w), 803 (w), 754 (w), 662 (w), 598 (m), 523 (m), 453 (m),
410 (w) cm–1. HRMS (ESI): calcd. for C15H22N2O7Na [M + Na]+
365.1319; found 365.1318.
FTIR (neat): ν = 3547 (w), 2984 (w), 2927 (w), 2862 (w), 2152 (w),
˜
1765 (w), 1734 (m), 1689 (m), 1648 (m), 1526 (w), 1437 (m),
1369 (w), 1367 (w), 1302 (w), 1215 (s), 1111 (m), 1018 (s), 970 (s),
857 (w), 823 (w), 791 (w), 702 (w), 658 (w), 599 (w), 533 (m), 4-Cyano-3-methyl-2-(morpholinocarbonyl)-5-oxo-N-(tosylmethyl)-
453 (w) cm–1. HRMS (ESI): calcd. for C16H27N2O9PNa [M +
Na]+ 445.1346; found 445.1347.
2,5-dihydrofuran-2-carboxamide (27a): Following general procedure
C in dichloromethane on a 0.54 mmol scale using 7b, after a reac-
Eur. J. Org. Chem. 2014, 993–1006
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