Hydrochloric Acid → HCID 67682958, compound

HRID 1751641Notes

Reaction equation

HRID 1751641 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3C(OC(C)(C)C)=O)=[N:10][CH:9]=2)=[CH:4][C:3]=1[C:25]#[C:26][CH3:27].Cl.[CH3:29][O:30][C:31]([NH:33][C@@H:34]([CH:38]([CH3:40])[CH3:39])[C:35](O)=[O:36])=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:35](=[O:36])[C@@H:34]([NH:33][C:31](=[O:32])[O:30][CH3:29])[CH:38]([CH3:40])[CH3:39])=[N:10][CH:9]=2)=[CH:4][C:3]=1[C:25]#[C:26][CH3:27]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 69675641HCID 69675641, compound

Product 1

HCID 67682958HCID 67682958, compoundYield 81.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-tert-butyl 2-(5-(4-bromo-3-(prop-1-ynyl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (400 mg, 0.98 mmol) was dissolved in DCM (8 mL), MeOH (2 mL) and HCl (4 M in dioxane, 2 mL) was added. The reaction mixture was stirred for 22 h and then concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (163 mg, 0.93 mmol), HATU (354 mg, 0.98 mmol) and DMF (10 mL), then DIPEA (0.81 mL, 4.65 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 gel chromatography (0% to 30% MeOH/EtOAc) to afford methyl (S)-1-((S)-2-(5-(4-bromo-3-(prop-1-ynyl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (369 mg, 81%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. waitAfter 2 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 silica gel chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-7aed58de6dbd4569a83e47c69e03688e
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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