(S)-1-(5-Methyl-1,3,4-oxadiazol-2-yl)-2-phenylethanamine → (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-(((S)-1-(5-methyl-1,3,4-oxadiazol-2-yl)-2-phenylethyl)carbamoyl)pyrrolidin-3-yl)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HRID 339276Notes

Reaction equation

O1C2C(=CC=CC=2)[C@H](NC([C@@H]2CC3C(=CC([C@H]4C[C@@H](C(=O)N[C@H]5C6C(=CC=CC=6)CCC5)N(C(=O)[C@@H](NC(=O)[C@@H](NC)C)C(C)(C)C)C4)=CC=3)CN2C(=O)[C@@H](NC(=O)[C@@H](NC)C)C(C)(C)C)=O)CC1.C(O[C:75]([N:77](C)[C@@H:78]([CH3:152])[C:79]([NH:81][C@@H:82]([C:148]([CH3:151])([CH3:150])[CH3:149])[C:83]([N:85]1[CH2:89][C@@H:88]([C:90]2[CH:99]=[C:98]3[C:93]([CH2:94][C@@H:95]([C:121](=[O:133])[NH:122][C@H:123]4[C:132]5[C:127](=[CH:128][CH:129]=[CH:130][CH:131]=5)[CH2:126][CH2:125][CH2:124]4)[N:96]([C:100](=[O:120])[C@@H:101]([NH:106][C:107](=[O:119])[C@@H:108]([N:110](C(OC(C)(C)C)=O)[CH3:111])[CH3:109])[C:102]([CH3:105])([CH3:104])[CH3:103])[CH2:97]3)=[CH:92][CH:91]=2)[CH2:87][C@H:86]1[C:134](N[C@@H](CC1C=CC=CC=1)C(O)=O)=[O:135])=[O:84])=[O:80])=O)(C)(C)C.[CH3:154][C:155]1[O:159][C:158]([C@@H:160]([NH2:168])[CH2:161][C:162]2[CH:167]=[CH:166][CH:165]=[CH:164][CH:163]=2)=[N:157][N:156]=1>>[CH3:105][C:102]([CH3:103])([CH3:104])[C@H:101]([NH:106][C:107](=[O:119])[C@@H:108]([NH:110][CH3:111])[CH3:109])[C:100]([N:96]1[C@H:95]([C:121]([NH:122][C@H:123]2[C:132]3[C:127](=[CH:128][CH:129]=[CH:130][CH:131]=3)[CH2:126][CH2:125][CH2:124]2)=[O:133])[CH2:94][C:93]2[C:98](=[CH:99][C:90]([C@H:88]3[CH2:87][C@@H:86]([C:134](=[O:135])[NH:168][C@H:160]([C:158]4[O:159][C:155]([CH3:154])=[N:156][N:157]=4)[CH2:161][C:162]4[CH:167]=[CH:166][CH:165]=[CH:164][CH:163]=4)[N:85]([C:83](=[O:84])[C@@H:82]([NH:81][C:79](=[O:80])[C@@H:78]([NH:77][CH3:75])[CH3:152])[C:148]([CH3:149])([CH3:150])[CH3:151])[CH2:89]3)=[CH:91][CH:92]=2)[CH2:97]1)=[O:120]

Participants

Reactant 3

HCID 42047875(S)-1-(5-Methyl-1,3,4-oxadiazol-2-yl)-2-phenylethanamine

HCID 86705911(S)-N-((R)-Chroman-4-yl)-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)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HCID 86705917(S)-2-((2S,4R)-1-((S)-2-((S)-2-((tert-Butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-4-((S)-2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-2-carboxamido)-3-phenylpropanoic acid2×

Product 1

HCID 86705920(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-(((S)-1-(5-methyl-1,3,4-oxadiazol-2-yl)-2-phenylethyl)carbamoyl)pyrrolidin-3-yl)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamideYield 53%

Procedure

Following procedures analogous to those for the preparation of Compounds F and G of Example 46, (S)-2-((2S,4R)-1-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-4-((S)-2-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-2-carboxamido)-3-phenylpropanoic acid (Compound D of Example 46, 50 mg, 0.049 mmol) and (S)-1-(5-methyl-1,3,4-oxadiazol-2-yl)-2-phenylethanamine (10 mg, 0.049 mmol) were converted to the title compound (26 mg, 53% over 2 steps). MS (ESI+) m/z 1001.8 (M+H)+.

Sources & evidence

ORD record: ord-ff4fd31e7d9643e8a86e258f2684d436
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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