(S)-1-((R)-2-(diethylamino)-2-phenylacetyl)-N-(4-(((4-fluorophenyl)(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenyl)pyrrolidine-2-carboxamide → N-(methoxycarbonyl)-O-methyl-L-threonyl-N-[4-({[4-({1-[(2R)-2-(diethylamino)-2-phenylacetyl]-L-prolyl}amino)benzyl](4-fluorophenyl)amino}methyl)phenyl]-L-prolinamide

HRID 923408Notes

Reaction equation

[CH2:1]([N:3]([CH2:51][CH3:52])[C@H:4]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C:12]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][C:31]([C@@H:33]3[CH2:37][CH2:36][CH2:35][NH:34]3)=[O:32])=[CH:26][CH:25]=2)=[CH:17][CH:16]=1)=[O:13])=[O:6])[CH3:2].[CH3:53][O:54][C@H:55]([CH3:65])[C@H:56]([NH:60][C:61]([O:63][CH3:64])=[O:62])[C:57](O)=[O:58]>>[CH3:64][O:63][C:61]([NH:60][C@H:56]([C:57]([N:34]1[CH2:35][CH2:36][CH2:37][C@H:33]1[C:31]([NH:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][N:22]([CH2:21][C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:12](=[O:13])[C@@H:8]3[CH2:9][CH2:10][CH2:11][N:7]3[C:5](=[O:6])[C@H:4]([N:3]([CH2:1][CH3:2])[CH2:51][CH3:52])[C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[CH:20][CH:19]=2)[C:38]2[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=2)=[CH:25][CH:26]=1)=[O:32])=[O:58])[C@@H:55]([CH3:65])[O:54][CH3:53])=[O:62]

Participants

Reactant 2

HCID 59540095(S)-1-((R)-2-(diethylamino)-2-phenylacetyl)-N-(4-(((4-fluorophenyl)(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenyl)pyrrolidine-2-carboxamide

HCID 59540170(2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid

Product 1

HCID 59540203N-(methoxycarbonyl)-O-methyl-L-threonyl-N-[4-({[4-({1-[(2R)-2-(diethylamino)-2-phenylacetyl]-L-prolyl}amino)benzyl](4-fluorophenyl)amino}methyl)phenyl]-L-prolinamideYield 40.1%

Procedure

The product from Example 81A (0.038 g, 0.054 mmol) and (2S,3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid (0.011 g, 0.059 mmol) were processed as in Example 81A to give 0.019 g (40%) of the title compound as an off-white solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 0.89 (t, J=7.10 Hz, 3 H) 1.07 (t, J=7.17 Hz, 2 H) 1.13 (d, J=6.26 Hz, 3 H) 1.28 (t, J=7.25 Hz, 1 H) 1.76-1.92 (m, 4 H) 1.94-2.05 (m, 2 H) 2.07-2.23 (m, 2 H) 2.39-2.46 (m, 2 H) 2.57-2.63 (m, 2 H) 3.24 (s, 3 H) 3.34-3.42 (m, 1 H) 3.43-3.50 (m, 1 H) 3.53 (s, 3 H) 3.63-3.70 (m, 1 H) 3.75-3.87 (m, 2 H) 3.97-4.03 (m, 1 H) 4.26 (t, J=7.78 Hz, 1 H) 4.36-4.46 (m, 2 H) 4.56 (s, 4 H) 4.67 (s, 1 H) 6.64 (dd, J=9.31, 4.43 Hz, 2 H) 6.89-6.95 (m, 2 H) 7.16-7.22 (m, 4 H) 7.28 (t, J=7.17 Hz, 1 H) 7.33 (t, J=7.40 Hz, 2 H) 7.40 (d, J=7.17 Hz, 1 H) 7.49-7.57 (m, 4 H) 7.66-7.70 (m, 1 H) 9.96 (d, J=7.02 Hz, 2 H); MS ESI− m/z 876.5.

Sources & evidence

ORD record: ord-43a084377edc40f0a65fdf47c940942c
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278922B2

Reaction notes

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