Hydrochloric Acid → HCID 178438798, compound

HRID 1751643Notes

Reaction equation

HRID 1751643 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:56]([CH3:58])[CH3:57])[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]5C(OC(C)(C)C)=O)=[N:34][C:30]=3[CH:29]=[CH:28]4)=[C:21]([C:53]#[C:54][CH3:55])[CH:20]=2)=[CH:17][N:18]=1)=[O:8])=[O:4].Cl.[CH3:60][O:61][C:62]([NH:64][C@H:65]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:66]([OH:68])=O)=[O:63].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>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:56]([CH3:58])[CH3:57])[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:66](=[O:68])[C@H:65]([NH:64][C:62](=[O:63])[O:61][CH3:60])[C:69]5[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=5)=[N:34][C:30]=3[CH:29]=[CH:28]4)=[C:21]([C:53]#[C:54][CH3:55])[CH:20]=2)=[CH:17][N:18]=1)=[O:8])=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178438799HCID 178438799, compound

Product 1

HCID 178438798HCID 178438798, compoundYield 21.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 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)-2-(prop-1-ynyl)phenyl)-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (66 mg, 0.084 mmol) was dissolved in DCM (2 mL), MeOH (0.5 mL) and HCl (4 M in dioxane, 0.5 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-(methoxycarbonylamino)-2-phenylacetic acid (18 mg, 0.084 mmol), COMU (40 mg, 0.084 mmol) and DMF (3 mL), then DIPEA (0.73 mL, 0.42 mmol) was added dropwise. After 15 h, 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 (R)-2-((2S,4S)-2-(7-(4-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-2-(prop-1-ynyl)phenyl)-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-2-oxo-1-phenylethylcarbamate (16 mg, 21%). LCMS-ESI+: calculated for C50H54N8O7: 878.41; observed [M+1]+: 879.60.

Workup

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 15 h
  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 HPLC

Sources & evidence

ORD record
ord-74b059d63c0f44c6b2d3e62fa7ec5c95
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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