(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-((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

HRID 339270Notes

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[CH2:67][C@@H:66]([C:68]2[CH:77]=[C:76]3[C:71]([CH2:72][C@@H:73]([C:99](=[O:111])[NH:100][C@H:101]4[C:110]5[C:105](=[CH:106][CH:107]=[CH:108][CH:109]=5)[CH2:104][CH2:103][CH2:102]4)[N:74]([C:78](=[O:98])[C@@H:79]([NH:84][C:85](=[O:97])[C@@H:86]([N:88]([C:90]([O:92][C:93]([CH3:96])([CH3:95])[CH3:94])=[O:91])[CH3:89])[CH3:87])[C:80]([CH3:83])([CH3:82])[CH3:81])[CH2:75]3)=[CH:70][CH:69]=2)[CH2:65][C@H:64]1[C:112]([NH:114][C@@H:115]([CH2:120][C:121]1[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=1)[C:116]([O:118]C)=[O:117])=[O:113])=[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[CH2:67][C@@H:66]([C:68]2[CH:77]=[C:76]3[C:71]([CH2:72][C@@H:73]([C:99](=[O:111])[NH:100][C@H:101]4[C:110]5[C:105](=[CH:106][CH:107]=[CH:108][CH:109]=5)[CH2:104][CH2:103][CH2:102]4)[N:74]([C:78](=[O:98])[C@@H:79]([NH:84][C:85](=[O:97])[C@@H:86]([N:88]([C:90]([O:92][C:93]([CH3:94])([CH3:96])[CH3:95])=[O:91])[CH3:89])[CH3:87])[C:80]([CH3:82])([CH3:81])[CH3:83])[CH2:75]3)=[CH:70][CH:69]=2)[CH2:65][C@H:64]1[C:112]([NH:114][C@@H:115]([CH2:120][C:121]1[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=1)[C:116]([OH:118])=[O:117])=[O:113])=[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 86705916(S)-Methyl 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-phenylpropanoate

Product 1

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 acidYield 96.2%

Procedure

Following a procedure analogous to that for the synthesis of Compound K of Example 1, (S)-methyl 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-phenylpropanoate (310 mg, 0.26 mmol) was converted to the title compound (291 mg, 95%). MS (ESI+) m/z 1016.7 (M+H)+.

Sources & evidence

ORD record: ord-4ca6e71b36c449f783d0d3233a7f762f
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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