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Helvetica Chimica Acta ± Vol. 83 (2000)
3025s, 2961s, 2930vs, 2870s, 1663vs, 1622vs, 1521vs, 1457vs, 1406vs, 1391vs, 1312s, 1296m, 1262s, 1234s, 1187s,
1
1091vs, 1053vs, 1032m, 988m, 958m, 905m, 874w, 836w, 802w, 762s, 740m, 709vs, 661s, 607m. H-NMR: 7.38 (s,
NH); 7.28 ± 7.21 (m, 3 arom. H); 7.09 ± 7.06 (m, 2 arom. H); 5.04 (t, J 5.0, OH); 3.37 ± 3.34 (m, CH2OH); 3.27,
3.06 (AB, J 13.5, PhCH2); 2.92 (br. s, Me2N); 1.28, 1.02 (2s, Me2C, PhCH2(Me)C). 13C-NMR: 174.8, 171.2 (2s, 2
CO); 137.1 (s, 1 arom. C); 130.8, 127.6, 126.2 (3d, 5 arom. C); 67.7 (t, CH2OH); 58.5, 43.1 (2s, Me2C,
PhCH2(Me)C); 41.0 (t, PhCH2); 37.4 (q, Me2N); 22.5, 22.4 (2q, Me2C, PhCH2(Me)C). CI-MS: 307 (24, [M
H] ), 262 (100, [M Me2N] ).
3. Hydrolysis of Dipeptide Amides 6. 3.1. 2-[(3-Hydroxy-1-oxo-2-phenylpropyl)amino]-2-methylpropanoic
Acid (7a). According to GP 3, 6a (1.37 g, 4.92 mmol), 25 ml of 3n HCl (H2O/THF 1:1), stirred for 42 h, H2O
(20 ml): 1.21 g (98%) of 7a. White powder. M.p. 212.4 ± 214.08. IR: 3298vs, 3227vs, 3062vs, 2929s, 2884s, 1710vs,
1650vs, 1557vs, 1490m, 1468s, 1454s, 1415m, 1380s, 1363m, 1345m, 1296s, 1272vs, 1235s, 1177s, 1088m, 1067m,
1051s, 1025s, 948s, 876w, 743m, 696vs, 622m, 604m. 1H-NMR: 12.05 (br. s, COOH); 8.17 (s, NH); 7.32 ± 7.18 (m, 5
arom. H); 4.68 (br. s, OH); 3.89 ± 3.83, 3.67 ± 3.62, 3.56 ± 3.50 (3m, CH2OH, CH); 1.35, 1.28 (2s, Me2C).
13C-NMR: 175.4, 170.9 (2s, 2 CO); 138.4 (s, 1 arom. C); 128.0, 127.9, 126.4 (3d, 5 arom. C); 63.6 (t, CH2OH); 54.7
(s, Me2C); 53.6 (d, CH); 24.80, 24.75 (2q, Me2C). ESI-MS: 274 (100, [M Na] ). Anal. calc. for C13H17NO4
(251.28): C 62.14, H 6.82, N 5.57; found: C 62.27, H 6.73, N 5.67.
3.2. 1-[(3-Hydroxy-1-oxo-2-phenylpropyl)amino]cyclopentanecarboxylic Acid (7b). According to GP 3, 6b
(1.657 g, 5.44 mmol), 6 ml of 3n HCl (H2O/THF 1:1), stirred for 24 h, H2O (20 ml): 1.491 g (99%) of 7b. M.p.
230.7 ± 231.28. IR: 3224vs, 3062vs, 2961vs, 2883s, 1707vs, 1648vs, 1559vs, 1490m, 1472m, 1455s, 1416s, 1377m,
1345m, 1309s, 1273vs, 1242m, 1193s, 1131w, 1093m, 1065s, 1049s, 1026s, 943m, 880w, 694vs, 603m. 1H-NMR: 12.00
(br. s, COOH); 8.25 (s, NH); 7.32 ± 7.17 (m, 5 arom. H); 3.90 ± 3.84, 3.68 ± 3.63, 3.57 ± 3.51 (3m, CH2OH, CH);
2.12 ± 1.73, 1.64 ± 1.52 (2m, (CH2)4). 13C-NMR: 175.2, 171.2 (2s, 2 CO); 138.4 (s, 1 arom. C); 128.0, 127.9, 126.4
(3d, 5 arom. C); 64.8 (s, (CH2)4C); 63.5 (t, CH2OH); 53.5 (d, CH); 36.2, 36.1, 23.92, 23.87 (4t, (CH2)4). CI-MS:
278 (100, [M H] ), 260 (56, [M OH] ), 232 (76, [M COOH] ). Anal. calc. for C15H19NO4 (277.32):
C 64.97, H 6.91, N 5.05; found: C 64.68, H 6.96, N 5.03.
3.3. 2-Benzyl-2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)amino]propanoic Acid (7c). According to GP 3, 6c
(2.52 g, 8.22 mmol), 40 ml 3N HCl (H2O/THF 1:1), stirred for 26 h, H2O (10 ml): 2.18 g (95%) of 7c. White
powder. M.p. 145.4 ± 146.08. IR: 3364vs, 3251vs, 2980vs, 1713vs, 1634vs, 1533vs, 1497s, 1457vs, 1406s, 1380s, 1367s,
1317s, 1290s, 1253vs, 1189vs, 1157s, 1128vs, 1092m, 1034vs, 995m, 936m, 911m, 885m, 826m, 789m, 753s, 734s,
1
700vs, 672s, 656vs, 607s. H-NMR: 12.69 (s, COOH); 7.48 (s, NH); 7.28 ± 7.20 (m, 3 arom. H); 7.10 ± 7.07 (m, 2
arom. H); 5.05 (br. s, OH); 3.35, 3.29 (AB, J 10.5, PhCH2); 3.20 (m, CH2OH); 1.37, 1.00, 0.99 (3s, Me2C,
PhCH2(Me)C). 13C-NMR: 175.7, 175.0 (2s, 2 CO); 136.8 (s, 1 arom. C); 130.1, 127.6, 126.3 (3d, 5 arom. C); 67.5
(t, CH2OH); 59.0, 42.8 (2s, Me2C, PhCH2(Me)C); 40.2 (t, PhCH2); 22.8, 22.4, 22.3 (3q, Me2C, PhCH2(Me)C).
CI-MS: 280 (100, [M H] ).
4. Reaction of 2H-Azirin-3-amines 5 with Dipeptides 7. 4.1. 2-({2-[(3-Hydroxy-1-oxo-2-phenylpropyl)ami-
no]-2-methyl-1-oxopropyl}amino)-2,N,N-trimethylpropanamide (8a). According to GP 1, 7a (1.133 g,
4.51 mmol) in MeCN (13 ml), 5a (0.508 g, 4.53 mmol) in MeCN (4 ml), stirred for 18 h: 1.537 g (94%) of 8a.
White powder. M.p. 185.7 ± 187.68. IR: 3440s, 3342vs, 3285vs, 3031m, 2987m, 2941m, 2850w, 1662vs, 1619vs,
1528vs, 1464m, 1398s, 1364s, 1318m, 1236m, 1209s, 1179m, 1122s, 1063s, 1029m, 971w, 898w, 767w, 739m, 701s,
640w, 610m. 1H-NMR: 8.17 (s, NH); 7.33 ± 7.23 (m, NH, 5 arom. H); 5.10 (br. s, OH); 3.93 ± 3.91, 3.75 ± 3.72,
3.61 ± 3.59 (3m, CH2OH, CH); 2.83 (br. s, Me2N); 1.34, 1.23, 1.22 (3s, 2 Me2C). 13C-NMR: 172.9, 171.6 (2s, 3
CO); 137.6 (s, 1 arom. C); 128.1, 127.9, 126.7 (3s, 5 arom. C); 63.9 (t, CH2OH); 56.3, 55.5 (2s, 2 Me2C); 53.8 (d,
CH); 37.2 (q, Me2N); 25.9, 25.4, 25.3, 24.3 (4q, 2 Me2C). ESI-MS: 386 (100, [M Na] ).
4.2. 1-{1-[(3-Hydroxy-1-oxo-2-phenylpropyl)amino]cyclopentanecarboxamido}-N,N-dimethylcyclopenta-
necarboxamide (8b). According to GP 1, 7b (1.431 g, 5.16 mmol) in MeCN (8 ml), 5c (0.812 g, 5.88 mmol) in
MeCN (2 ml), stirred for 25 h: 1.932 g (90%) of 8b. M.p. 233.4 ± 234.08. IR: 3463s, 3322vs, 3280vs, 3050m, 2957s,
2871s, 1655vs, 1620vs, 1524vs, 1456s, 1396s, 1330m, 1234m, 1064s, 1016m, 909w, 741m, 700s, 668m. 1H-NMR: 8.20
(s, NH); 7.39 ± 7.21 (m, 1 NH, 5 arom. H); 5.17 (t, J 4.3, OH); 3.96 ± 3.88, 3.77 ± 3.72, 3.65 ± 3.59 (3m, CH2OH,
CH); 2.78 (br. s, Me2N); 2.11 ± 1.85, 1.72 ± 1.49 (2m, 2 (CH2)4). 13C-NMR: 172.24, 172.18 171.4 (3s, 3 CO); 137.5
(s, 1 arom. C); 128.1, 127.9, 126.8 (3d, 5 arom. C); 66.5, 65.5 (2s, 2 (CH2)4C); 63.7 (t, CH2OH); 53.8 (d, CH); 37.1
(q, Me2N); 36.8, 36.2, 35.9, 35.3, 23.83, 23.75, 23.6 (7t, 2 (CH2)4). CI-MS: 371 (25, [M H] ), 371 (100, [M
Me2N] ).
4.3.
2-({2-Benzyl-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)amino]-1-oxopropyl}amino)-2,N-dimethyl-N-
phenylpropanamide (8c). According to GP 2, 7c (0.999 g, 3.58 mmol) in MeCN (15 ml), 5b (0.632 g, 3.63 mmol)
in MeCN (2 ml), stirred for 2 h, CC (SiO2, CH2Cl2/MeOH 20 :1): 1.419 g (87%) of 8c. Colorless foam. IR:
3854w, 3341s, 3029w, 2984m, 2873m, 1636vs, 1594s, 1495vs, 1456s, 1391s, 1364s, 1240m, 1201m, 1116m, 1092s,