Hydrochloric Acid → HCID 178502308, compound

HRID 1751426Notes

Reaction equation

HRID 1751426 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 47.2%

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 (1.10 g, 2.64 mmol) was dissolved in DCM (15 mL) and HCl (4M in dioxane, 3 mL) was added. After stirring for 2.5 h, the reaction mixture was concentrated and the residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (462 mg, 2.64 mmol), HATU (1.003 g, 2.64 mmol) and DMF (13 mL). The stirred mixture was cooled to 0° C. and DIPEA (2.3 mL, 13.2 mmol) was added. After 7 min, the reaction was allowed to warm to RT. 20 min later, the mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (79% to 100% EtOAc/hexane) to afford the title compound (590 mg, 47%).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. waitAfter 7 min
  3. temperatureto warm to RT
  4. washwashed with saturated aqueous NaHCO3 and brine
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica column chromatography (79% to 100% EtOAc/hexane)

Sources & evidence

ORD record
ord-2aa4b5d8be7c46beb8da1dd8c386385b
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…