Hydrogen Bromide → HCID 86708755, compound

HRID 1751530Notes

Reaction equation

HRID 1751530 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]4[CH:18]=[CH:17][C:16]([C:19]5[NH:23][C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6C(OCC6C=CC=CC=6)=O)=[N:21][CH:20]=5)=[CH:15][C:11]4=[CH:12][CH:13]=3)[O:8][CH2:7][C:6]=2[CH:39]=1.Br.[CH3:41][O:42][C:43]([NH:45][C@@H:46]([CH:50]([CH3:52])[CH3:51])[C:47](O)=[O:48])=[O:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>C(OCC)(=O)C.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[C:10]4[CH:18]=[CH:17][C:16]([C:19]5[NH:23][C:22]([C@@H:24]6[CH2:28][CH2:27][CH2:26][N:25]6[C:47](=[O:48])[C@@H:46]([NH:45][C:43](=[O:44])[O:42][CH3:41])[CH:50]([CH3:52])[CH3:51])=[N:21][CH:20]=5)=[CH:15][C:11]4=[CH:12][CH:13]=3)[O:8][CH2:7][C:6]=2[CH:39]=1

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 79724-MethylmorpholineHCID 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 86708756HCID 86708756, compound

Product 1

HCID 86708755HCID 86708755, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-benzyl 2-(5-(8-bromo-6H-dibenzo[c,h]chromen-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (485 mg, 0.84 mmol), hydrogen bromide (33% in acetic acid, 1 mL) and dichloromethane (2 mL) was stirred at room temperature for one hour. The reaction was concentrated, suspended in toluene, sonicated for one minute and re-concentrated. The resulting residue was suspended in methanol, sonicated for one minute and concentrated. The resulting residue was suspended in diethyl ether and the solids collected by filtration. This crude amine was dissolved in dimethylformamide (7 mL). To this solution were added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (192 mg, 1.1 mmol), HATU (418 mg, 1.1 mmol) and N-methylmorpholine (0.24 mL, 2.2° mmol). The reaction was stirred at room temperature for one hour, and then diluted ethyl acetate. The organic layer was washed with 5% aqueous LiCl solution, saturated aqueous NaHCO3 solution and brine, then dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield methyl (S)-1-((S)-2-(5-(8-bromo-6H-dibenzo[c,h]chromen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (466 mg, 92%).

Workup

  1. concentrationThe reaction was concentrated
  2. customsonicated for one minute
  3. concentrationre-concentrated
  4. customsonicated for one minute
  5. concentrationconcentrated
  6. filtrationthe solids collected by filtration
  7. dissolutionThis crude amine was dissolved in dimethylformamide (7 mL)
  8. washThe organic layer was washed with 5% aqueous LiCl solution, saturated aqueous NaHCO3 solution and brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-6394428ab46143e693902a66ea73e394
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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