Hydrochloric Acid → HCID 178495678, compound

HRID 1751632Notes

Reaction equation

HRID 1751632 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:53]([CH3:55])[CH3:54])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:26]=[C:27]4[C:50](=[CH:51][CH:52]=3)[C:31]3[NH:32][C:33]([C@@H:35]5[CH2:39][C@H:38]([CH2:40][O:41][CH3:42])[CH2:37][N:36]5[C:43](OC(C)(C)C)=[O:44])=[N:34][C:30]=3[CH:29]=[CH:28]4)=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:8])=[O:4].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(O)=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>C(Cl)Cl.CO.CCOC(C)=O.CN(C=O)C>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:53]([CH3:55])[CH3:54])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]1[NH:15][C:16]([C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:26]=[C:27]4[C:50](=[CH:51][CH:52]=3)[C:31]3[NH:32][C:33]([C@@H:35]5[CH2:39][C@H:38]([CH2:40][O:41][CH3:42])[CH2:37][N:36]5[C:43](=[O:44])[C@H:62]([NH:61][C:59](=[O:60])[O:58][CH3:57])[C:66]5[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=5)=[N:34][C:30]=3[CH:29]=[CH:28]4)=[CH:23][CH:24]=2)=[CH:17][N:18]=1)=[O:8])=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178495679HCID 178495679, compound

Product 1

HCID 178495678HCID 178495678, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

(2S,4S)-tert-butyl 2-(7-(4-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (140 mg, 0.187 mmol) was dissolved in DCM (5 mL) and HCl (4 M in dioxane, 1 mL, 4 mmol) was added. After stirring for 1.5 h, the reaction mixture was concentrated under reduced pressure. The crude residue was treated with (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (43 mg, 0.206 mmol), COMU (80 mg, 0.187 mmol), DMF (3 mL) and DIPEA (0.33 mL, 1.9 mmol). After stirring at RT for 20 min, the solution was diluted with 30 mL 10% MeOH/EtOAc. The organic layer was washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica column chromatography to afford methyl {(1R)-2-[(2S,4S)-2-[7-(4-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)-1H-naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl}carbamate (106 mg, 68%). MS (ESI) m/z 841 [M+H]+.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. stirringAfter stirring at RT for 20 min
  3. washThe organic layer was washed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica column chromatography

Sources & evidence

ORD record
ord-f028c84b8f1a4a3c9a8f75e4c01c16eb
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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