Hydrochloric Acid → HCID 178495669, compound

HRID 1751629Notes

Reaction equation

HRID 1751629 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:27](=[CH:28][CH:29]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][C@H:15]([CH2:17][O:18][CH3:19])[CH2:14][N:13]3[C:20](OC(C)(C)C)=[O:21])=[N:11][C:7]=1[CH:6]=[CH:5]2.Cl.[CH3:31][O:32][C:33]([NH:35][CH:36]([CH:40]([CH3:42])[CH3:41])C(O)=O)=[O:34].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:27](=[CH:28][CH:29]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][C@H:15]([CH2:17][O:18][CH3:19])[CH2:14][N:13]3[C:20](=[O:21])[C@@H:36]([NH:35][C:33](=[O:34])[O:32][CH3:31])[CH:40]([CH3:42])[CH3:41])=[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 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178495670HCID 178495670, compound

Product 1

HCID 178495669HCID 178495669, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (526 mg, 1.14 mmol) was dissolved in DCM (15 mL) and HCl (4 M in dioxane, 3 mL, 12 mmol) was added. The reaction mixture was stirred for 2 h and then concentrated under reduced pressure. The crude residue was treated with (methoxycarbonylamino)-3-methylbutanoic acid (220 mg, 1.25 mmol), HATU (433 mg, 1.14 mmol) and DMF (11 mL), then cooled to 0° C. DIPEA (0.99 mL, 5.7 mmol) was added dropwise and the reaction mixture was immediately warmed to RT. After 45 min at RT, the mixture was diluted with EtOAc (100 mL) and washed successively with saturated aqueous NaHCO3, water 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 methyl (S)-1-((2S,4S)-2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (584 mg, 99%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. temperaturethe reaction mixture was immediately warmed to RT
  3. waitAfter 45 min at RT
  4. washwashed successively with saturated aqueous NaHCO3, water and brine
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc)

Sources & evidence

ORD record
ord-5f91b401dc5944b28cd8b72d54a7f816
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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