(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 → (2S,4S)-1-((Benzyloxy)carbonyl)-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-tetrahydroisoquinoline-7-carboxamido)pyrrolidine-2-carboxylic acid

HRID 339239Notes

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]([CH3:113])[C@@H:56]([CH3:112])[C:57]([NH:59][C@@H:60]([C:108]([CH3:111])([CH3:110])[CH3:109])[C:61]([N:63]1[C@H:72]([C:73](=[O:85])[NH:74][C@H:75]2[C:84]3[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=3)[CH2:78][CH2:77][CH2:76]2)[CH2:71][C:70]2[C:65](=[CH:66][C:67]([C:86]([NH:88][C@@H:89]3[CH2:93][N:92]([C:94]([O:96][CH2:97][C:98]4[CH:103]=[CH:102][CH:101]=[CH:100][CH:99]=4)=[O:95])[C@H:91]([C:104]([O:106]C)=[O:105])[CH2:90]3)=[O:87])=[CH:68][CH:69]=2)[CH2:64]1)=[O:62])=[O:58])=[O:54])([CH3:51])([CH3:50])[CH3:49]>>[CH2:97]([O:96][C:94]([N:92]1[CH2:93][C@@H:89]([NH:88][C:86]([C:67]2[CH:66]=[C:65]3[C:70]([CH2:71][C@@H:72]([C:73](=[O:85])[NH:74][C@H:75]4[C:84]5[C:79](=[CH:80][CH:81]=[CH:82][CH:83]=5)[CH2:78][CH2:77][CH2:76]4)[N:63]([C:61](=[O:62])[C@@H:60]([NH:59][C:57](=[O:58])[C@@H:56]([N:55]([C:53]([O:52][C:48]([CH3:49])([CH3:51])[CH3:50])=[O:54])[CH3:113])[CH3:112])[C:108]([CH3:109])([CH3:110])[CH3:111])[CH2:64]3)=[CH:69][CH:68]=2)=[O:87])[CH2:90][C@H:91]1[C:104]([OH:106])=[O:105])=[O:95])[C:98]1[CH:103]=[CH:102][CH:101]=[CH:100][CH:99]=1

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 86705871(2S,4S)-1-Benzyl 2-methyl 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-tetrahydroisoquinoline-7-carboxamido)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 86705872(2S,4S)-1-((Benzyloxy)carbonyl)-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-tetrahydroisoquinoline-7-carboxamido)pyrrolidine-2-carboxylic acidYield 99.5%

Procedure

Following a procedure analogous to that for the synthesis of Compound K, (2S,4S)-1-benzyl 2-methyl 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-tetrahydroisoquinoline-7-carboxamido)pyrrolidine-1,2-dicarboxylate (192 mg, 0.21 mmol) was converted to the title compound (187 mg, 99%). MS (ESI+) m/z 895.5 (M+H)+.

Sources & evidence

ORD record: ord-ca3d4eee4e4c4041999469ff2f160c2c
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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