Hydrochloric Acid → methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate

HRID 1751581Notes

Reaction equation

HRID 1751581 reaction equation
[Br:1][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12]([O:14]C(C)(C)C)=O)=[N:4][CH:3]=1.Cl.[CH3:20][O:21][C:22]([NH:24][C@@H:25]([CH:29]([CH3:31])[CH3:30])C(O)=O)=[O:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CO.C(OCC)(=O)C>[Br:1][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12](=[O:14])[C@@H:25]([NH:24][C:22](=[O:23])[O:21][CH3:20])[CH:29]([CH3:31])[CH3:30])=[N:4][CH:3]=1

Participants

8

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 56605192tert-Butyl (2S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

Product 1

HCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.0 g, 3.2 mmol), 4M HCl solution in dioxanes (3.95 mL, 15.8 mmol) and methanol (4 mL) was stirred at room temperature for thirty minutes. The reaction was concentrated, suspended in dichloromethane, and thoroughly concentrated. This crude amine was dissolved in dimethylformamide (6.4 mL). To this solution were added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (582 mg, 3.3 mmol), HATU (1.3 g, 3.3 mmol) and diisopropylethylamine (1.9 mL, 11.1 mmol). The reaction was stirred at room temperature for twenty minutes, and then diluted with ethyl acetate. The organic layer was washed with water and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (985 mg, 83%).

Workup

  1. concentrationThe reaction was concentrated
  2. concentrationthoroughly concentrated
  3. dissolutionThis crude amine was dissolved in dimethylformamide (6.4 mL)
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-0c1db6ed910e4c299fb9573ed777fec3
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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