Sodium Carbonate → HCID 66869409, compound

HRID 250769Notes

Reaction equation

HRID 250769 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][C:5]2=[N:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1.[CH2:17]([N:21]1[C:25]2[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:24]=2[N:23]=[C:22]1[NH2:33])[CH:18]([CH3:20])[CH3:19].C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:17]([N:21]1[C:25]2[CH:26]=[C:27]([C:2]3[N:6]4[CH2:7][CH2:8][CH2:9][C:5]4=[N:4][C:3]=3[C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:28]=[CH:29][C:24]=2[N:23]=[C:22]1[NH2:33])[CH:18]([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 14076484HCID 14076484, compoundHCID 66868816HCID 66868816, compound

Product 1

HCID 66869409HCID 66869409, compoundYield 31.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Bubble nitrogen through a solution of 3-bromo-2-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (750 mg, 2.67 mmol) in dimethoxyethane (20 ml). Add bis(triphenylphosphine)palladium(II) chloride (175 mg, 0.095 mmol) and stir at room temperature for 3 minutes. Add (1-isobutyl-2-amino-1H-benzimidazol-6-yl)boronic acid (750 mg, 3.211 mmol) by 2M aqueous sodium carbonate (2.7 mL, 5.40 mmol). Heat at 90° C. for 16 hours. Cool to room temperature, dilute with water (50 ml), and extract with ethyl acetate (150 ml). Dry over magnesium sulfate and concentrate under reduced pressure. Subject the residue to HPLC (Xterra MS C18 5 μm, 19×100 mm; Solvent A: 10 mM ammonium carbonate at pH 9; Solvent B: acetonitrile; Gradient: from 35 to 50% B in 8 minutes and then 50 95% B in 1 minute; Flow rate: 20 mL/min) to provide 1-isobutyl-2-amino-6-(2-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-1H-benzimidazole (325 mg, 31%). MS (ES): m/z=390 (M++H) The free base is treated with two equivalents of methanesulfonic acid essentially as previously described to provide the title compound (50%).

Workup

  1. temperatureCool to room temperature
  2. extractionextract with ethyl acetate (150 ml)
  3. dry with materialDry over magnesium sulfate
  4. concentrationconcentrate under reduced pressure
  5. wait50 95% B in 1 minute

Sources & evidence

ORD record
ord-fd5ac2426330444dac1407d0556fd577
Source dataset
uspto-grants-2011_01
Patent number
US07863310B2

Reaction notes

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