Hydrochloric Acid → HCID 67682124, compound

HRID 1751646Notes

Reaction equation

HRID 1751646 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:52]([CH3:54])[CH3:53])[C:7]([N:9]1[CH2:13][C@@H:12]([CH2:14][O:15][CH3:16])[CH2:11][C@H:10]1[C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]4[NH:38][C:37]([C@@H:39]5[CH2:43][C@H:42]([CH3:44])[CH2:41][N:40]5C(OC(C)(C)C)=O)=[N:36][CH:35]=4)=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)=[CH:20][N:21]=1)=[O:8])=[O:4].Cl.[C:56]([O:60][C:61]([NH:63][C@H:64]([C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)[C:65]([OH:67])=O)=[O:62])([CH3:59])([CH3:58])[CH3:57].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.CCOC(C)=O.CN(C=O)C.CO>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:52]([CH3:54])[CH3:53])[C:7]([N:9]1[CH2:13][C@@H:12]([CH2:14][O:15][CH3:16])[CH2:11][C@H:10]1[C:17]1[NH:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]4[NH:38][C:37]([C@@H:39]5[CH2:43][C@H:42]([CH3:44])[CH2:41][N:40]5[C:65](=[O:67])[C@H:64]([NH:63][C:61](=[O:62])[O:60][C:56]([CH3:57])([CH3:58])[CH3:59])[C:68]5[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=5)=[N:36][CH:35]=4)=[CH:30][CH:29]=3)=[CH:26][CH:27]=2)=[CH:20][N:21]=1)=[O:8])=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 86708798HCID 86708798, compound

Product 1

HCID 67682124HCID 67682124, compoundYield 74%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,4S)-tert-butyl 2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (342 mg, 0.46 mmol) was dissolved in DCM (4 mL), MeOH (1 mL) and HCl (4 M in dioxane, 1 mL) was added. The reaction mixture was stirred over night and then concentrated under reduced pressure. The crude residue was treated with (R)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (116 mg, 0.46 mmol), COMU (220 mg, 0.64 mmol) and DMF (5 mL), then DIPEA (0.4 mL, 2.31 mmol) was added dropwise. After 2 h, the mixture was diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford tert-butyl (R)-2-((2S,4S)-2-(5-(4′-(2-((2S,4S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamate (296 mg, 74%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed successively with saturated aqueous NaHCO3 and brine
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-963a9637696d4adfa3187e2b69afa2a3
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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