Sodium Bicarbonate → (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

HRID 625598Notes

Reaction equation

HRID 625598 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7](Cl)[CH:6]=[N:5]2.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[CH:23][C:24]3[N:28]=[C:27]([C@@H:29]4[CH2:34][C@@H:33]5[C@@H:31]([CH2:32]5)[N:30]4[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[NH:26][C:25]=3[CH:42]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CO.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>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:22]1[CH:21]=[CH:42][C:25]3[N:26]=[C:27]([C@@H:29]4[CH2:34][C@@H:33]5[C@@H:31]([CH2:32]5)[N:30]4[C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[NH:28][C:24]=3[CH:23]=1)[CH:6]=[N:5]2

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 126864086-Bromo-2-chloroquinoxalineHCID 58498658(1R,3S,5R)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 1

HCID 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-carboxylateYield 82.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Pd(Ph3P)4 (28.5 mg, 0.025 mmol) was added to a degassed solution of 6-bromo-2-chloroquinoxaline (60 mg, 0.246 mmol), (1R,3S,5R)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (115 mg, 0.271 mmol) and sodium bicarbonate (62.1 mg, 0.739 mmol) in dioxane (1 mL) and H2O (0.2 mL) and the mixture was stirred at 110° C. for 2 h and then at 120° C. for 2 h. The reaction was diluted with MeOH, filtered and purified by prep HPLC (H2O-MeOH with 10 mM NH4OAc buffer) to yield (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 (102.2 mg, 0.202 mmol, 82% yield) as bright yellow solid. LC-MS retention time 2.31 min; m/z 506 [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. waitat 120° C. for 2 h
  2. filtrationfiltered
  3. custompurified by prep HPLC (H2O-MeOH with 10 mM NH4OAc buffer)

Sources & evidence

ORD record
ord-b706802c18b24e6aaaaa01c74ef5a121
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

Loading…