N-(Methoxycarbonyl)-L-tert-leucine → N-(methoxycarbonyl)-3-methyl-L-valyl-N-[4-({[4-({1-[(2R)-2-(diethylamino)-2-phenylacetyl]-L-prolyl}amino)benzyl](4-fluorophenyl)amino}methyl)phenyl]-L-prolinamide

HRID 923406Notes

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:55]([NH:57][C@@H:58]([C:62]([CH3:65])([CH3:64])[CH3:63])[C:59](O)=[O:60])=[O:56]>>[CH3:53][O:54][C:55]([NH:57][C@H:58]([C:59]([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:60])[C:62]([CH3:63])([CH3:64])[CH3:65])=[O:56]

Participants

Reactant 2

HCID 11263950N-(Methoxycarbonyl)-L-tert-leucine

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

Product 1

HCID 59540304N-(methoxycarbonyl)-3-methyl-L-valyl-N-[4-({[4-({1-[(2R)-2-(diethylamino)-2-phenylacetyl]-L-prolyl}amino)benzyl](4-fluorophenyl)amino}methyl)phenyl]-L-prolinamideYield 59%

Procedure

The product from Example 81A (0.042 g, 0.060 mmol) and (S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid (0.013 g, 0.066 mmol) were processed as in Example 81A to give 0.031 g (59%) of the title compound as an off-white solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 0.88 (t, J=7.10 Hz, 6 H) 0.95 (s, 9 H) 1.76-1.89 (m, 4 H) 1.93-2.00 (m, 2 H) 2.02-2.10 (m, 1 H) 2.10-2.18 (m, 1 H) 2.40-2.47 (m, 2 H) 2.56-2.65 (m, 2 H) 3.52 (s, 3 H) 3.61 (dd, J=17.24, 7.48 Hz, 2 H) 3.73-3.80 (m, 2 H) 4.20 (d, J=9.00 Hz, 1 H) 4.37 (dd, J=7.93, 4.27 Hz, 1 H) 4.42 (dd, J=7.78, 5.19 Hz, 1 H) 4.54 (s, 4 H) 4.66 (s, 1 H) 6.63 (dd, J=9.31, 4.43 Hz, 2 H) 6.90 (t, J=8.85 Hz, 2 H) 7.07 (d, J=8.85 Hz, 1 H) 7.17 (dd, J=8.47, 3.89 Hz, 4 H) 7.26 (t, J=7.17 Hz, 1 H) 7.32 (t, J=7.40 Hz, 2 H) 7.39 (d, J=7.17 Hz, 2 H) 7.50 (dd, J=8.39, 6.10 Hz, 4 H) 9.95 (s, 1 H) 9.99 (s, 1 H); MS ESI+ m/z 876.5.

Sources & evidence

ORD record: ord-a335dc821fcd48018999613d07bb22fa
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278922B2

Reaction notes

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