Hydrochloric Acid → HCID 67682437, compound

HRID 1751647Notes

Reaction equation

HRID 1751647 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:62]([CH3:64])[CH3:63])[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]5[C:45](=[O:61])[C@H:46]([NH:53][C:54](=O)[O:55]C(C)(C)C)[C:47]5[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=5)=[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.[CH:66]1(C(O)=O)[CH2:68][CH2:67]1.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.CO>[CH:66]1([C:54]([NH:53][C@H:46]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:45]([N:40]2[CH2:41][C@@H:42]([CH3:44])[CH2:43][C@H:39]2[C:37]2[NH:38][C:34]([C:31]3[CH:32]=[CH:33][C:28]([C:25]4[CH:24]=[CH:23][C:22]([C:19]5[NH:18][C:17]([C@@H:10]6[CH2:11][C@H:12]([CH2:14][O:15][CH3:16])[CH2:13][N:9]6[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:62]([CH3:64])[CH3:63])=[N:21][CH:20]=5)=[CH:27][CH:26]=4)=[CH:29][CH:30]=3)=[CH:35][N:36]=2)=[O:61])=[O:55])[CH2:68][CH2:67]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 67682124HCID 67682124, compoundHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 67682437HCID 67682437, compoundYield 28.9%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

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, 0.33 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 cyclopropanecarboxylic acid (38 μL, 0.28 mmol), COMU (162 mg, 0.34 mmol) and DMF (4 mL), then DIPEA (0.29 mL, 1.65 mmol) was added dropwise. After 30 min, the mixture was diluted with 10% MeOH/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 HPLC to afford methyl (S)-1-((2S,4S)-2-(5-(4′-(2-((2S,4S)-1-((R)-2-(cyclopropanecarboxamido)-2-phenylacetyl)-4-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (68 mg, 24%). LCMS-ESI+: calculated for C48H56N8O6: 840.43; observed [M+1]+: 842.14.

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 HPLC

Sources & evidence

ORD record
ord-7848875dd7bc4c24b11b4ed093823130
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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