Hydrochloric Acid → HCID 86708801, compound

HRID 1751661Notes

Reaction equation

HRID 1751661 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:52]([CH3:54])[CH3:53])[C:7]([N:9]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[NH:36][C:35]([C@@H:37]5[CH2:41][C@H:40]([CH2:42][O:43][CH3:44])[CH2:39][N:38]5C(OC(C)(C)C)=O)=[N:34][CH:33]=4)=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)=[CH:18][N:19]=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](O)=[O:66])=[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[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]1[NH:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[NH:36][C:35]([C@@H:37]5[CH2:41][C@H:40]([CH2:42][O:43][CH3:44])[CH2:39][N:38]5[C:65](=[O:66])[C@H:64]([NH:63][C:61](=[O:62])[O:60][C:56]([CH3:57])([CH3:59])[CH3:58])[C:68]5[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=5)=[N:34][CH:33]=4)=[CH:28][CH:27]=3)=[CH:24][CH:25]=2)=[CH:18][N:19]=1)=[O:8])=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 67682163HCID 67682163, compoundHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 86708801HCID 86708801, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,4S)-tert-butyl 2-(5-(4′-(2-((2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (289 mg, 0.39 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 for 2 h and then concentrated under reduced pressure. The crude residue was treated with (R)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (98 mg, 0.39 mmol), COMU (186 mg, 0.39 mmol) and DMF (5 mL), then DIPEA (0.34 mL, 1.96 mmol) was added dropwise. After 30 min, 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,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamate (201 mg, 59%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 30 min
  3. washwashed 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 crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-7d970b100ee44770aa0b5c2739e231ab
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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