Hydrochloric Acid → HCID 69675030, compound

HRID 1431836Notes

Reaction equation

HRID 1431836 reaction equation
[I:1][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][C@H:9]([CH3:12])[N:8]2[C:13]([O:15]C(C)(C)C)=O)=[N:4][CH:3]=1.Cl.[CH3:21][O:22][C:23]([NH:25][C@@H:26]([CH:30]([CH3:32])[CH3:31])C(O)=O)=O.[CH3:33]N(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>ClCCl>[I:1][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:11][CH2:10][C@H:9]([CH3:12])[N:8]2[C:13](=[O:15])[C@@H:26]([NH:25][C:23]([O:22][CH3:21])=[CH2:33])[CH:30]([CH3:32])[CH3:31])=[N:4][CH:3]=1

Participants

7

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 69675660HCID 69675660, compound

Product 1

HCID 69675030HCID 69675030, compoundYield 94.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A round bottom flask was charged with (2S,5S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (1.5 g, 3.98 mmol) and treated with an excess of hydrochloric acid (100 mL of 4.0M in dioxane). The mixture was stirred vigorously for 3 hours in which time a precipitate formed and the solvent was removed in vacuo. To a mixture of the crude intermediate, (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.836 g, 4.77 mmol), HATU (1.81 g, 4.77 mmol) in dichloromethane (25 mL), diisopropylethylamine (3.46 mL, 19.9 mmol) was then added dropwise and was stirred over night under nitrogen. The reaction mixture was partitioned ethyl acetate and saturated sodium bicarbonate. The organic layer was dried with sodium sulfate, the solvent removed in vacuo. The crude product was purified by column chromatography to yield (2S)-1-[(2S,5S)-2-(5-iodo-1H-imidazol-2-yl)-5-methylpyrrolidin-1-yl]-2-[(1-methoxyethenyl)amino]-3-methylbutan-1-one as a white solid (1.63 g, 3.75 mmol, 94%). LCMS-ESI+: calc'd for C15H23IN4O3: 434.08 (M+). Found: 435.51 (M+H+).

Workup

  1. customformed
  2. customthe solvent was removed in vacuo
  3. additionwas then added dropwise
  4. stirringwas stirred over night under nitrogen
  5. customThe reaction mixture was partitioned ethyl acetate and saturated sodium bicarbonate
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. customthe solvent removed in vacuo
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-5e983efd7cfc413caae2a7b8252eb16f
Source dataset
uspto-grants-2015_01
Patent number
US08940718B2

Reaction notes

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