Diisopropylethylamine → HCID 178502358, compound

HRID 1625500Notes

Reaction equation

HRID 1625500 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]=[C:17]([C@@H:20]4[CH2:24][CH2:23][CH2:22][NH:21]4)[NH:18][CH:19]=3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:25][O:26][C:27]([NH:29][C@@H:30]([CH:34]([CH3:36])[CH3:35])[C:31](O)=[O:32])=[O:28].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.C([O-])(O)=O.[Na+]>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[N:16]=[C:17]([C@@H:20]4[CH2:24][CH2:23][CH2:22][N:21]4[C:31](=[O:32])[C@@H:30]([NH:29][C:27](=[O:28])[O:26][CH3:25])[CH:34]([CH3:36])[CH3:35])[NH:18][CH:19]=3)=[CH:13][CH:14]=2)=[CH:7][CH:8]=1

Participants

7

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 178419344HCID 178419344, compound

Product 1

HCID 178502358HCID 178502358, compoundYield 84.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (S)-4-(4′-bromo-[1,1′-biphenyl]-4-yl)-2-(pyrrolidin-2-yl)-1H-imidazole hydrochloride (423 mg, 1.045 mmol) in DMF (5 mL) is sequentially added (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (201.5 mg, 1.150 mmol), DIPEA (405.2 mg, 546.1 μL, 3.135 mmol) and HATU (596.2 mg, 1.568 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 2 hours and diluted with saturated aqueous NaHCO3 (10 mL). The reaction mixture is extracted with EtOAc (5×10 mL), and the combined organic layer are washed with H2O (3×10 mL), and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (2 to 20% methanol in CH2Cl2) to give methyl ((S)-1-((S)-2-(4-(4′-bromo-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (462 mg, 84%).

Workup

  1. extractionThe reaction mixture is extracted with EtOAc (5×10 mL)
  2. washthe combined organic layer are washed with H2O (3×10 mL)
  3. concentrationconcentrated to dryness
  4. customThe residue is purified by flash column chromatography on silica gel (2 to 20% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-4139dc6e0b5a4dce8bdc7a2747454f67
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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