Morpholine → (S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-7-((3R,5S)-1-((S)-3,3-dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N-((S)-1-morpholino-1-oxo-3-phenylpropan-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HRID 339266Notes

Reaction equation

C(OC([N:8]([CH3:84])[C@@H:9]([CH3:83])[C:10]([NH:12][C@@H:13]([C:79]([CH3:82])([CH3:81])[CH3:80])[C:14]([N:16]1[C@H:25]([C:26]([NH:28][C@@H:29]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:30](O)=[O:31])=[O:27])[CH2:24][C:23]2[C:18](=[CH:19][C:20]([C@H:40]3[CH2:44][C@@H:43]([C:45](=[O:57])[NH:46][C@H:47]4[C:56]5[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=5)[CH2:50][CH2:49][CH2:48]4)[N:42]([C:58](=[O:78])[C@@H:59]([NH:64][C:65](=[O:77])[C@@H:66]([N:68]([C:70](OC(C)(C)C)=O)C)[CH3:67])[C:60]([CH3:63])([CH3:62])[CH3:61])[CH2:41]3)=[CH:21][CH:22]=2)[CH2:17]1)=[O:15])=[O:11])=O)(C)(C)C.[NH:85]1[CH2:90][CH2:89][O:88][CH2:87][CH2:86]1>>[CH3:82][C:79]([CH3:80])([CH3:81])[C@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([NH:8][CH3:84])[CH3:83])[C:14]([N:16]1[C@H:25]([C:26]([NH:28][C@@H:29]([CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:30]([N:85]2[CH2:90][CH2:89][O:88][CH2:87][CH2:86]2)=[O:31])=[O:27])[CH2:24][C:23]2[C:18](=[CH:19][C:20]([C@H:40]3[CH2:44][C@@H:43]([C:45](=[O:57])[NH:46][C@H:47]4[C:56]5[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=5)[CH2:50][CH2:49][CH2:48]4)[N:42]([C:58](=[O:78])[C@@H:59]([NH:64][C:65](=[O:77])[C@@H:66]([NH:68][CH3:70])[CH3:67])[C:60]([CH3:63])([CH3:62])[CH3:61])[CH2:41]3)=[CH:21][CH:22]=2)[CH2:17]1)=[O:15]

Participants

Reactant 2

HCID 8083Morpholine

HCID 86705906(S)-2-((S)-2-((S)-2-((S)-2-((tert-Butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-7-((3R,5S)-1-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamido)-3-phenylpropanoic acid2×

Product 1

HCID 86705908(S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-7-((3R,5S)-1-((S)-3,3-dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N-((S)-1-morpholino-1-oxo-3-phenylpropan-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamideYield 37%

Procedure

Following procedures analogous to those described for the preparation of Example 42, (S)-2-((S)-2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-7-((3R,5S)-1-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamido)-3-phenylpropanoic acid (Compound B of Example 41, 25 mg, 0.021 mmol) and morpholine (Aldrich, 3 mg, 0.032 mmol) were converted to the title compound (8 mg, 37% over 2 steps). MS (ESI+) m/z 1032.7 (M+H)+.

Sources & evidence

ORD record: ord-239fbbaf273349a0bf16cb273b66bbdf
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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