Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamate → [1-(2-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl]-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 72010Notes

Reaction equation

HRID 72010 reaction equation
[CH3:1][O:2][C:3](=[O:61])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=CC=[C:26]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[NH:38][C:39]([C@@H:42]6[CH2:46][CH2:45][CH2:44][N:43]6[C:47](=[O:60])[CH:48]([NH:55][C:56]([O:58][CH3:59])=[O:57])[C:49]6[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=6)=[N:40][CH:41]=5)=[CH:33][CH:32]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].COC(=O)N[CH:66](C(N1CCCC1C1NC(C2C=CC(Br)=CC=2)=CN=1)=O)[CH:67](C)C.C(OC(N1CCCC1C1NC(C2C=CC3C(=CC=C(B4OC(C)(C)C(C)(C)O4)C=3)C=2)=CN=1)=O)(C)(C)C>>[CH3:1][O:2][C:3](=[O:61])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:22]=[CH:23][C:28]([C:27]3[CH:67]=[CH:66][C:32]4[C:31](=[CH:36][CH:35]=[C:34]([C:37]5[NH:38][C:39]([CH:42]6[CH2:46][CH2:45][CH2:44][N:43]6[C:47](=[O:60])[CH:48]([NH:55][C:56]([O:58][CH3:59])=[O:57])[C:49]6[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=6)=[N:40][CH:41]=5)[CH:33]=4)[CH:26]=3)=[CH:29][CH:30]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

4

Reactant 3

HCID 66620141Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamateHCID 66620205[1-(2-{5-[6-(4-{2-[1-(2 S)-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterHCID 666205222-{5-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66620728[1-(2-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl]-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterYield 54%

Procedure

This compound was prepared following the procedure for [1-(2-{5-[6-(4-{2-[1-(2S)-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl}-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester using (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.0 g, 2.2 mmol) and 2-{5-[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.6 g, 3.4 mmol, 1.5 equiv.) to provide [1-(2-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.03 g, 54%) as a white powder. LCMS-ESI+: calc'd for C47H50N8O6: 822.4 (M+). Found: 823.9 (M+H+). 1H-NMR: 400 MHz, (CDCl3) δ: (Mixture of rotomers) 7.52-7.93 (m, 9H), 7.27-7.42 (m, 6H), 7.16 (s, 2H), 6.08 (m, 1H), 5.48-5.56 (m, 2H), 5.34 (s, 1H), 5.24 (s, 1H), 4.35 (t, 1H), 3.93 (m, 1H), 3.73 (m, 1H), 3.68 (s, 3H), 3.66 (s, 3H), 3.38 (m, 1H), 2.78-2.83 (m, 3H), 2.36 (m, 1H), 2.04-2.23 (m, 6H), 0.86-0.97 (m, 6H).

Workup

  1. customThis compound was prepared

Sources & evidence

ORD record
ord-ef14b85895934a1d9ac9669739f59c2e
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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