Bromide ion → (R)-4-(4-(1H-imidazol-1-yl)phenyl)-3-amino-1-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one

HRID 1096653Notes

Reaction equation

HRID 1096653 reaction equation
[Br-].Br[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C@@H:10]([NH:34]C(=O)OC(C)(C)C)[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH2:17][C@@H:16]([C:20]3[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[C:23]4[CH:30]=[CH:31][CH:32]=[CH:33][C:22]=4[N:21]=3)[CH2:15]2)=[O:13])=[CH:5][CH:4]=1.[NH:42]1[CH:46]=[CH:45][N:44]=[CH:43]1.CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[N:42]1([C:3]2[CH:4]=[CH:5][C:6]([CH2:9][C@@H:10]([NH2:34])[CH2:11][C:12]([N:14]3[CH2:19][CH2:18][CH2:17][C@@H:16]([C:20]4[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[C:23]5[CH:30]=[CH:31][CH:32]=[CH:33][C:22]=5[N:21]=4)[CH2:15]3)=[O:13])=[CH:7][CH:8]=2)[CH:46]=[CH:45][N:44]=[CH:43]1

Participants

8

Reactant 5

HCID 259Bromide ionHCID 795ImidazoleHCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 66791560tert-butyl (R)-1-(4-bromophenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate

Product 1

HCID 66786089(R)-4-(4-(1H-imidazol-1-yl)phenyl)-3-amino-1-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of bromide, tert-butyl (R)-1-(4-bromophenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (prepared from the procedure of Example 6, Step A) (45 mg, 0.088 mmol), imidazole (11 mg, 2 eq), CuI (3.3 mg, 20% mol), N,N′-dimethylethylenediamine (3.1 mg, 40% mol), potassium phosphate (K3PO4) (37.4 mg, 2 eq) in 2 mL dioxane was heated at 110° C. for 27 hrs. The mixture was filtered; the filtrate was washed with EtOAc and concentrated to give a greenish oil.

Workup

  1. filtrationThe mixture was filtered
  2. washthe filtrate was washed with EtOAc
  3. concentrationconcentrated
  4. customto give a greenish oil

Sources & evidence

ORD record
ord-a8984d92d1584b3895b1a374b590ae64
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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