Trifluoroacetic acid → HCID 178484886, compound

HRID 339272Notes

Reaction equation

O1C2C(=CC=CC=2)[C@H]([NH:11][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.C(OC(N(C)[C@@H](C)C(N[C@@H](C(C)(C)C)C(N1C[C@@H](C2C=C3C(C[C@@H](C(=O)N[C@H]4C5C(=CC=CC=5)CCC4)N(C(=O)[C@@H](NC(=O)[C@@H](N(C(OC(C)(C)C)=O)C)C)C(C)(C)C)C3)=CC=2)C[C@H]1C(N[C@@H](CC1C=CC=CC=1)C(O)=O)=O)=O)=O)=O)(C)(C)C.[C:154]1([CH2:160][C@@H:161]([C:163]2[NH:167][N:166]=[N:165][N:164]=2)N)[CH:159]=[CH:158][CH:157]=[CH:156][CH:155]=1.C(O)(C(F)(F)F)=O>>[CH3:46][C:44]([CH3:47])([CH3:45])[C@H:43]([NH:48][C:49](=[O:54])[C@@H:50]([NH:52][CH3:53])[CH3:51])[C:42]([N:26]1[CH:27]([C:29]([NH:30][C@H:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][CH2:33][CH2:32]2)=[O:41])[CH2:18][C:19]2[C:24](=[CH:28][C:22]([C@H:17]3[CH2:23][C@@H:14]([C:12](=[O:13])[NH:11][C@H:161]([C:163]4[NH:167][N:166]=[N:165][N:164]=4)[CH2:160][C:154]4[CH:159]=[CH:158][CH:157]=[CH:156][CH:155]=4)[N:15]([C:56](=[O:69])[C@@H:57]([NH:62][C:63](=[O:68])[C@@H:64]([NH:66][CH3:67])[CH3:65])[C:58]([CH3:59])([CH3:61])[CH3:60])[CH2:16]3)=[CH:21][CH:20]=2)[CH2:25]1)=[O:55]

Participants

Reactant 4

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-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×

HCID 178511764HCID 178511764, compound

Product 1

HCID 178484886HCID 178484886, compoundYield 33%

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, 30 mg, 0.030 mmol) and (S)-2-phenyl-1-(1H-tetrazol-5-yl)ethanamine, TFA (17 mg, 0.059 mmol) were converted to the title compound (10 mg, 33% over 2 steps). MS (ESI+) m/z 987.8 (M+H)+.

Sources & evidence

ORD record: ord-11ebd21f764a4af9bed723f1deb345c4
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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