(S)-2-((Methoxycarbonyl)amino)butanoic acid → methyl [(1S)-1-({(2S)-2-[(4-{[(4-fluorophenyl){4-[({(2S)-1-[(2R)-2-phenyl-2-piperidin-1-ylacetyl]pyrrolidin-2-yl]carbonyl)amino]benzyl}amino]methyl}phenyl)carbamoyl]pyrrolidin-1-yl}carbonyl)propyl]carbamate

HRID 923423Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([C@@H:34]3[CH2:38][CH2:37][CH2:36][N:35]3[C:39](=[O:53])[C@@H:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[N:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)=[O:33])=[CH:27][CH:26]=2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([C@@H:19]3[CH2:23][CH2:22][CH2:21][NH:20]3)=[O:18])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[CH3:54][O:55][C:56]([NH:58][C@@H:59]([CH2:63][CH3:64])[C:60](O)=[O:61])=[O:57]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]([C@@H:19]3[CH2:23][CH2:22][CH2:21][N:20]3[C:60]([C@@H:59]([NH:58][C:56](=[O:57])[O:55][CH3:54])[CH2:63][CH3:64])=[O:61])=[O:18])=[CH:12][CH:11]=2)[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([C@@H:34]3[CH2:38][CH2:37][CH2:36][N:35]3[C:39](=[O:53])[C@@H:40]([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[N:41]3[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]3)=[O:33])=[CH:27][CH:26]=2)=[CH:4][CH:3]=1

Participants

Reactant 2

HCID 10012186(S)-2-((Methoxycarbonyl)amino)butanoic acid

HCID 59540252(S)-N-(4-(((4-fluorophenyl)(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenyl)-1-((R)-2-phenyl-2-(piperidin-1-yl)acetyl)pyrrolidine-2-carboxamide

Product 1

HCID 59540219methyl [(1S)-1-({(2S)-2-[(4-{[(4-fluorophenyl){4-[({(2S)-1-[(2R)-2-phenyl-2-piperidin-1-ylacetyl]pyrrolidin-2-yl]carbonyl)amino]benzyl}amino]methyl}phenyl)carbamoyl]pyrrolidin-1-yl}carbonyl)propyl]carbamate

Procedure

The product from Example 114C (0.040 g, 0.056 mmol) and (S)-2-(methoxycarbonylamino)butanoic acid (0.011 g, 0.067 mmol) were processed as in Example 81A to give the title compound. 1H NMR (400 MHz, DMSO-D6) δ ppm 0.90 (t, J=7.37 Hz, 3 H) 1.29-1.37 (m, 2 H) 1.39-1.47 (m, 4 H) 1.47-1.58 (m, 1 H) 1.61-1.72 (m, 1 H) 1.75-2.06 (m, 6 H) 2.08-2.20 (m, 1 H) 3.39-3.50 (m, 1 H) 3.52 (s, 3 H) 3.56-3.64 (m, 1 H) 3.69-3.77 (m, 1 H) 3.79-3.90 (m, 1 H) 4.14-4.21 (m, 1 H) 4.24 (s, 1 H) 4.31 (dd, J=7.81, 4.23 Hz, 1 H) 4.43 (dd, J=7.92, 4.34 Hz, 1 H) 4.56 (s, 4 H) 6.64 (dd, J=9.27, 4.39 Hz, 2 H) 6.91 (t, J=8.89 Hz, 2 H) 7.17 (dd, J=8.51, 2.55 Hz, 4 H) 7.27-7.36 (m, 3 H) 7.42 (d, J=6.94 Hz, 2 H) 7.51 (dd, J=8.51, 3.74 Hz, 4 H) 9.95 (d, J=2.93 Hz, 2 H); MS ESI− m/z 858.6 (M−H)−.

Sources & evidence

ORD record: ord-f890688fa0254e109db5ab48dab3caa2
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278922B2

Reaction notes

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