(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-tetrahydroisoquinoline-7-carboxylic acid → (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

HRID 339265Notes

Reaction equation

C(OC(N(C)[C@@H](C)C(N[C@@H](C(C)(C)C)C(N1[C@H](C(=O)N[C@H]2C3C(=CC=CC=3)CCC2)CC2C(=CC(C(O)=O)=CC=2)C1)=O)=O)=O)(C)(C)C.[C:48]([O:52][C:53]([N:55]([CH3:132])[C@@H:56]([CH3:131])[C:57]([NH:59][C@@H:60]([C:127]([CH3:130])([CH3:129])[CH3:128])[C:61]([N:63]1[C@H:72]([C:73]([NH:75][C@@H:76]([CH2:81][C:82]2[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=2)[C:77]([O:79]C)=[O:78])=[O:74])[CH2:71][C:70]2[C:65](=[CH:66][C:67]([C@H:88]3[CH2:92][C@@H:91]([C:93](=[O:105])[NH:94][C@H:95]4[C:104]5[C:99](=[CH:100][CH:101]=[CH:102][CH:103]=5)[CH2:98][CH2:97][CH2:96]4)[N:90]([C:106](=[O:126])[C@@H:107]([NH:112][C:113](=[O:125])[C@@H:114]([N:116]([C:118]([O:120][C:121]([CH3:124])([CH3:123])[CH3:122])=[O:119])[CH3:117])[CH3:115])[C:108]([CH3:111])([CH3:110])[CH3:109])[CH2:89]3)=[CH:68][CH:69]=2)[CH2:64]1)=[O:62])=[O:58])=[O:54])([CH3:51])([CH3:50])[CH3:49]>>[C:48]([O:52][C:53]([N:55]([CH3:132])[C@@H:56]([CH3:131])[C:57]([NH:59][C@@H:60]([C:127]([CH3:130])([CH3:129])[CH3:128])[C:61]([N:63]1[C@H:72]([C:73]([NH:75][C@@H:76]([CH2:81][C:82]2[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=2)[C:77]([OH:79])=[O:78])=[O:74])[CH2:71][C:70]2[C:65](=[CH:66][C:67]([C@H:88]3[CH2:92][C@@H:91]([C:93](=[O:105])[NH:94][C@H:95]4[C:104]5[C:99](=[CH:100][CH:101]=[CH:102][CH:103]=5)[CH2:98][CH2:97][CH2:96]4)[N:90]([C:106](=[O:126])[C@@H:107]([NH:112][C:113](=[O:125])[C@@H:114]([N:116]([C:118]([O:120][C:121]([CH3:124])([CH3:123])[CH3:122])=[O:119])[CH3:117])[CH3:115])[C:108]([CH3:109])([CH3:111])[CH3:110])[CH2:89]3)=[CH:68][CH:69]=2)[CH2:64]1)=[O:62])=[O:58])=[O:54])([CH3:49])([CH3:50])[CH3:51]

Participants

Reactant 2

HCID 86705870(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-tetrahydroisoquinoline-7-carboxylic acid

HCID 86705907(S)-methyl 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-phenylpropanoate

Product 1

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 acidYield 60%

Procedure

Following a procedure analogous to that for the synthesis of Compound K of Example 1, (S)-methyl 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-phenylpropanoate (290 mg, 0.25 mmol) was converted to the title compound (172 mg, 60%). MS (ESI+) m/z 1163.9 (M+H)+.

Sources & evidence

ORD record: ord-f28d3726337a4d409fcb6f4fae368c89
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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