Trifluoroacetic acid → (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-(5-methyl-1,2,4-oxadiazol-3-yl)-2-phenylethyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

HRID 339268Notes

Reaction equation

O1C2C(=CC=CC=2)[C@H](N[C:12]([C@@H:14]2[CH2:23][C:22]3[C:17](=[CH:18][C:19]([C@H:24]4[CH2:28][C@@H:27]([C:29](=[O:41])[NH:30][C@H:31]5[C:40]6[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=6)[CH2:34][CH2:33][CH2:32]5)[N:26]([C:42](=[O:55])[C@@H:43]([NH:48][C:49](=[O:54])[C@@H:50]([NH:52][CH3:53])[CH3:51])[C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:25]4)=[CH:20][CH:21]=3)[CH2:16][N:15]2[C:56](=[O:69])[C@@H:57]([NH:62][C:63](=[O:68])[C@@H:64]([NH:66][CH3:67])[CH3:65])[C:58]([CH3:61])([CH3:60])[CH3:59])=[O:13])CC1.[CH3:70][C:71]1[O:75][N:74]=[C:73]([C@@H:76]([NH2:84])[CH2:77][C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[N:72]=1.C(O)(C(F)(F)F)=O>>[CH3:61][C:58]([CH3:59])([CH3:60])[C@H:57]([NH:62][C:63](=[O:68])[C@@H:64]([NH:66][CH3:67])[CH3:65])[C:56]([N:15]1[C@H:14]([C:12]([NH:84][C@H:76]([C:73]2[N:72]=[C:71]([CH3:70])[O:75][N:74]=2)[CH2:77][C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)=[O:13])[CH2:23][C:22]2[C:17](=[CH:18][C:19]([C@H:24]3[CH2:28][C@@H:27]([C:29](=[O:41])[NH:30][C@H:31]4[C:40]5[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=5)[CH2:34][CH2:33][CH2:32]4)[N:26]([C:42](=[O:55])[C@@H:43]([NH:48][C:49](=[O:54])[C@@H:50]([NH:52][CH3:53])[CH3:51])[C:44]([CH3:45])([CH3:46])[CH3:47])[CH2:25]3)=[CH:20][CH:21]=2)[CH2:16]1)=[O:69]

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

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-carboxamide2×

HCID 86705913(S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)-2-phenylethanamine

Product 1

HCID 86705912(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-(5-methyl-1,2,4-oxadiazol-3-yl)-2-phenylethyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamideYield 33%

Procedure

Following procedures analogous to those described for the preparation of Example 33, (S)-2-(tert-butoxycarbonyl)-7-((3R,5S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Compound F of Example 33, 60 mg, 0.10 mmol) and (S)-1-(5-methyl-1,2,4-oxadiazol-3-yl)-2-phenylethanamine, TFA (31 mg, 0.10 mmol) were converted to the title compound (34 mg, 33% over 6 steps). MS (ESI+) m/z 1001.7 (M+H)+.

Sources & evidence

ORD record: ord-5651c19afe0843758c979639aa35762b
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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