Methyl (S)-3,3-dimethyl-1-oxo-1-((S)-2-(4-((phenyl(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenylcarbamoyl)pyrrolidin-1-yl)butan-2-ylcarbamate → N-(methoxycarbonyl)-3-methyl-L-valyl-N-(4-{[{4-[(1-{(2S)-2-[(methoxycarbonyl)amino]-2-[(3R)-tetrahydrofuran-3-yl]acetyl}-L-prolyl)amino]benzyl}(phenyl)amino]methyl}phenyl)-L-prolinamide

HRID 923395Notes

Reaction equation

[CH3:1][C:2]([CH3:49])([CH3:48])[C@H:3]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C:4](=[O:42])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10](=[O:41])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([C@@H:30]3[CH2:34][CH2:33][CH2:32][NH:31]3)=[O:29])=[CH:23][CH:22]=2)=[CH:14][CH:13]=1.[CH3:50][O:51][C:52]([NH:54][C@@H:55]([C@H:59]1[CH2:63][CH2:62][O:61][CH2:60]1)[C:56](O)=[O:57])=[O:53]>>[CH3:46][O:45][C:44]([NH:43][C@H:3]([C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][N:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:29])[C@@H:30]3[CH2:34][CH2:33][CH2:32][N:31]3[C:56](=[O:57])[C@@H:55]([NH:54][C:52]([O:51][CH3:50])=[O:53])[C@H:59]3[CH2:63][CH2:62][O:61][CH2:60]3)=[CH:23][CH:22]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[CH:16][CH:17]=1)=[O:41])=[O:42])[C:2]([CH3:49])([CH3:48])[CH3:1])=[O:47]

Participants

Reactant 2

HCID 59540386Methyl (S)-3,3-dimethyl-1-oxo-1-((S)-2-(4-((phenyl(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenylcarbamoyl)pyrrolidin-1-yl)butan-2-ylcarbamate

HCID 66630452(S)-2-(methoxycarbonylamino)-2-((R)-tetrahydrofuran-3-yl)acetic acid

Product 1

HCID 59540101N-(methoxycarbonyl)-3-methyl-L-valyl-N-(4-{[{4-[(1-{(2S)-2-[(methoxycarbonyl)amino]-2-[(3R)-tetrahydrofuran-3-yl]acetyl}-L-prolyl)amino]benzyl}(phenyl)amino]methyl}phenyl)-L-prolinamideYield 67%

Procedure

The product of Example 10A (0.035 g, 0.052 mmol) and (S)-2-(methoxycarbonylamino)-2-((R)-tetrahydrofuran-3-yl)acetic acid were processed as in Example 25B to give 0.030 g (67%) of the title compound as a thick oil. 1H NMR (500 MHz, DMSO-D6) δ ppm 0.91 (s, 9 H) 1.66 (ddd, J=20.03, 7.21, 7.10 Hz, 1 H) 1.77-1.88 (m, 6 H) 1.90-1.99 (m, 2 H) 2.06-2.14 (m, 2 H) 3.48 (s, 6 H) 3.54-3.65 (m, 4 H) 3.66-3.75 (m, 3 H) 3.78-3.85 (m, 1 H) 4.14-4.22 (m, 2 H) 4.38 (dd, J=8.09, 5.04 Hz, 2 H) 4.53 (s, 4 H) 6.51 (t, J=7.25 Hz, 1 H) 6.60 (d, J=8.09 Hz, 2 H) 6.99-7.06 (m, 3 H) 7.12 (d, J=7.48 Hz, 4 H) 7.45 (d, J=7.93 Hz, 4 H) 7.55 (d, J=7.93 Hz, 1 H) 9.93 (d, J=6.26 Hz, 2 H); MS ESI− m/z 852.5 (M−H)−.

Sources & evidence

ORD record: ord-fbdee87c39f84945b478c03713df6657
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278922B2

Reaction notes

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