Hydrochloric Acid → Methyl (R)-2-((S)-2-(5-(4-(6-(2-((2S,4S)-4-hydroxy-1-((S)-2-(methoxycarbonylamino)-3-methyl butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamate

HRID 1751331Notes

Reaction equation

HRID 1751331 reaction equation
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:17])[C@@H:8]([NH:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]([CH3:11])[CH3:10])[C@H:4]([C:18]2[NH:19][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[CH:29]=[C:28]([C:33]3[CH:38]=[CH:37][C:36]([C:39]5[NH:43][C:42]([C@@H:44]6[CH2:48][CH2:47][CH2:46][N:45]6C(OC(C)(C)C)=O)=[N:41][CH:40]=5)=[CH:35][CH:34]=3)[CH:27]=[CH:26]4)=[CH:21][N:22]=2)[CH2:3]1.Cl.[CH3:57][O:58][C:59]([NH:61][C@H:62]([C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C:63]([OH:65])=O)=[O:60].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO>[OH:1][C@@H:2]1[CH2:6][N:5]([C:7](=[O:17])[C@@H:8]([NH:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]([CH3:11])[CH3:10])[C@H:4]([C:18]2[NH:19][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[CH:29]=[C:28]([C:33]3[CH:38]=[CH:37][C:36]([C:39]5[NH:43][C:42]([C@@H:44]6[CH2:48][CH2:47][CH2:46][N:45]6[C:63](=[O:65])[C@H:62]([NH:61][C:59](=[O:60])[O:58][CH3:57])[C:66]6[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=6)=[N:41][CH:40]=5)=[CH:35][CH:34]=3)[CH:27]=[CH:26]4)=[CH:21][N:22]=2)[CH2:3]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 86708705HCID 86708705, compound

Product 1

HCID 67681949Methyl (R)-2-((S)-2-(5-(4-(6-(2-((2S,4S)-4-hydroxy-1-((S)-2-(methoxycarbonylamino)-3-methyl butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamateYield 22.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To (S)-tert-butyl 2-(5-(4-(6-(2-((2S,4S)-4-hydroxy-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (61 mg, 0.082 mmol) in MeOH (2.5 mL) was added HCl (4M in dioxane, 0.5 mL). The solution stirred o/n, and the solvent was removed. The intermediate was dissolved in DMF (2 mL). (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (19 mg, 0.09 mmol), COMU (39 mg, 0.082 mmol), and DIPEA (0.07 mL, 0.41 mmol) were added sequentially. The solution was stirred o/n and the mixture was purified by HPLC to yield product (15.5 mg). LCMS-ESI+: calc'd for C47H50N8O7: 838.95 (M+); Found: 839.29 (M+H+).

Workup

  1. customwas removed
  2. dissolutionThe intermediate was dissolved in DMF (2 mL)
  3. stirringThe solution was stirred o/n and the mixture
  4. customwas purified by HPLC

Sources & evidence

ORD record
ord-5e54df604a344589960d38ce80ae667d
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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