Potassium Acetate → 2-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-6-ylboronic acid

HRID 625599Notes

Reaction equation

HRID 625599 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[CH:14][C:15]3[N:19]=[C:18]([C@@H:20]4[CH2:25][C@@H:24]5[C@@H:22]([CH2:23]5)[N:21]4[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[NH:17][C:16]=3[CH:33]=1)[CH:6]=[N:5]2.CC([O-])=O.[K+].[B:39]1(B2OC(C)(C)C(C)(C)O2)[O:43]C(C)(C)C(C)(C)[O:40]1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:29]([O:28][C:26]([N:21]1[C@H:20]([C:18]2[NH:17][C:16]3[CH:33]=[C:12]([C:7]4[CH:6]=[N:5][C:4]5[C:9](=[CH:10][CH:11]=[C:2]([B:39]([OH:43])[OH:40])[CH:3]=5)[N:8]=4)[CH:13]=[CH:14][C:15]=3[N:19]=2)[CH2:25][C@@H:24]2[C@H:22]1[CH2:23]2)=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 66982221(1R,3S,5R)-tert-butyl 3-(6-(6-bromoquinoxalin-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 1

HCID 669821792-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-6-ylboronic acidYield 60.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
83 °C

Procedure

Pd(Ph3P)4 (23.28 mg, 0.020 mmol) was added to a degassed solution of (1R,3S,5R)-tert-butyl 3-(6-(6-bromoquinoxalin-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (102 mg, 0.201 mmol), KOAc (49.4 mg, 0.504 mmol) and bis(pinacolato)diboron (113 mg, 0.443 mmol) in dioxane (2 mL) and the reaction was stirred at 83° C. for 16 h. The reaction mixture was partitioned between EtOAc (20 mL) and sat. NH4Cl(aq.) (5 mL). The organic layer was dried (MgSO4), filtered and concentrated to an orange oil, which was purified by prep HPLC (H2O-MeOH with 0.1% TFA buffer) to yield 2-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-6-yl)quinoxalin-6-ylboronic acid (57 mg, 0.121 mmol, 60.0% yield) as orange solid. LC-MS retention time 1.94 min; m/z 472 [M+H]+. (Column PHENOMENEX® Luna 3.0×50 mm S10. Solvent A=90% water: 10% methanol: 0.1% TFA. Solvent B=10% water: 90% methanol: 0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (20 mL) and sat. NH4Cl(aq.) (5 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to an orange oil, which
  5. customwas purified by prep HPLC (H2O-MeOH with 0.1% TFA buffer)

Sources & evidence

ORD record
ord-6bcbc31ad2d64323b9ee3fada9c78c66
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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