Hydrochloric Acid → HCID 178502451, compound

HRID 1625524Notes

Reaction equation

HRID 1625524 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7](O)=[O:8])=[O:4].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.[I:46][C:47]1[N:48]=[C:49]([C@@H:52]2[CH2:56][C@H:55]([CH3:57])[CH2:54][NH:53]2)[NH:50][CH:51]=1.Cl>CN(C=O)C.CCOC(C)=O.O>[I:46][C:47]1[N:48]=[C:49]([C@@H:52]2[CH2:56][C@H:55]([CH3:57])[CH2:54][N:53]2[C:7]([C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:10]([CH3:12])[CH3:11])=[O:8])[NH:50][CH:51]=1

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 1784615734-iodo-2-[(2S,4S)-4-methylpyrrolidin-2-yl]-1H-imidazole

Product 1

HCID 178502451HCID 178502451, compoundYield 87.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (644.5 mg, 3.68 mmol) in DMF (25 mL) at 0° C. is added HATU (1.4 g, 3.68 mmol), DIPEA (2.5 mL, 14.57 mmol) followed by 4-iodo-2-[(2S,4S)-4-methylpyrrolidin-2-yl]-1H-imidazole as HCl salt (1.28 g, 3.64 mmol). The reaction mixture is stirred at rt for 20 hours, diluted with EtOAc and H2O. The organic phase is separated, washed with H2O, dried over Na2SO4, filtered and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 100% EtOAC/Hexane) to afford methyl N-[(1S)-1-[(2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (1.3 g, 87.3%) as a white solid.

Workup

  1. customThe organic phase is separated
  2. washwashed with H2O
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue is purified by flash column chromatography on silica gel (0 to 100% EtOAC/Hexane)

Sources & evidence

ORD record
ord-1ae00e50f43f4ba2b0b69ae7ec013d39
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

Loading…