Diisopropylethylamine → HCID 178502346, compound

HRID 1625530Notes

Reaction equation

HRID 1625530 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].OC(C(F)(F)F)=O.[I:20][C:21]1[CH:34]=[CH:33][C:24]2[NH:25][C:26]([C@@H:28]3[CH2:32][CH2:31][CH2:30][NH:29]3)=[N:27][C:23]=2[CH:22]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[I:20][C:21]1[CH:34]=[CH:33][C:24]2[NH:25][C:26]([C@@H:28]3[CH2:32][CH2:31][CH2:30][N:29]3[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:10]([CH3:12])[CH3:11])=[N:27][C:23]=2[CH:22]=1

Participants

6

Reactant 4

HCID 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 178506537HCID 178506537, compound

Product 1

HCID 178502346HCID 178502346, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (S)-2-methoxycarbonylamino-3-methyl-butyric acid (68 mg, 0.39 mmol) and (S)-5-iodo-2-(pyrrolidin-2-yl)-1H-benzo[d]imidazole-TFA salt (100 mg, 0.32 mmol) in anhydrous DMF (2 mL) is added DIPEA (0.25 mL, 1.43 mmol) followed by HATU (142 mg, 0.37 mmol). The reaction mixture is stirred for 4 hours at room temperature. Ice is added and the product is extracted with EtOAc. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated in vacuum. The residue is purified by flash column chromatography on silica gel (EtOAc/MeOH 0% to 10%) to give methyl ((S)-1-((S)-2-(5-iodo-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (150 mg).

Workup

  1. additionIce is added
  2. extractionthe product is extracted with EtOAc
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuum
  6. customThe residue is purified by flash column chromatography on silica gel (EtOAc/MeOH 0% to 10%)

Sources & evidence

ORD record
ord-4e0d8712b98646a994cb86d72d626052
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

Loading…