Hydrochloric Acid → HCID 178502308, compound

HRID 1751628Notes

Reaction equation

HRID 1751628 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:24](=[CH:25][CH:26]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3C(OC(C)(C)C)=O)=[N:11][C:7]=1[CH:6]=[CH:5]2.Cl.[CH3:28][O:29][C:30]([NH:32][C@@H:33]([CH:37]([CH3:39])[CH3:38])[C:34](O)=[O:35])=[O:31].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>[Br:1][C:2]1[CH:3]=[C:4]2[C:24](=[CH:25][CH:26]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:34](=[O:35])[C@@H:33]([NH:32][C:30](=[O:31])[O:29][CH3:28])[CH:37]([CH3:39])[CH3:38])=[N:11][C:7]=1[CH:6]=[CH:5]2

Participants

9

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 178451893(S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 178502308HCID 178502308, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (1.50 g, 3.60 mmol) was dissolved in DCM (25 mL) and HCl (4 M solution in dioxane, 5 mL, 20 mmol) was added at once. After stirring for 3 h, the solution was concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (631 mg, 3.60 mmol), HATU (1.37 g, 3.60 mmol) and DMF (18 mL). The stirred solution was cooled to 0° C. and DIPEA (1.9 mL, 10 mmol) was added dropwise. After stirring for 20 min, the reaction mixture was warmed to RT. After an additional 10 min, it was diluted with EtOAc (150 mL) 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 33% MeOH/EtOAc) to afford the title compound (1.70 g, 100%).

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. stirringAfter stirring for 20 min
  3. temperaturethe reaction mixture was warmed to RT
  4. waitAfter an additional 10 min
  5. washwashed successively with saturated aqueous NaHCO3 and brine
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc)

Sources & evidence

ORD record
ord-4c0010ac41254ef5a7552bbe387e9c58
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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