Hydrochloric Acid → HCID 178502347, compound

HRID 1751423Notes

Reaction equation

HRID 1751423 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[CH2:6][CH2:5]2.Cl.[CH3:28][O:29][C:30]([NH:32][C@@H:33]([CH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1)[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]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[N:11][C:7]=1[CH2:6][CH2:5]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 59264488(S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 178451906HCID 178451906, compound

Product 1

HCID 178502347HCID 178502347, compoundYield 54.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-tert-butyl 2-(7-bromo-4,5-dihydro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (314 mg, 0.750 mmol) was dissolved in DCM (5 mL) and HCl (4M in dioxane, 1 mL) was added. After stirring for 1 h, the reaction mixture was concentrated and the residue was treated with (S)-2-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (163 mg, 0.750 mmol), HATU (285 mg, 0.750 mmol) and DMF (4 mL). After cooling to 0° C., DIPEA (0.65 mL, 3.75 mmol) was added dropwise and the reaction mixture was allowed to warm to RT. After 4 h, the mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford the title compound (211 mg, 54%).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. temperatureto warm to RT
  3. waitAfter 4 h
  4. washwashed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-219041f8a1f546679a9e2d3a5806bb0c
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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