1,2-Dimethoxyethane → (R)-4-((R)-1-((3-cyclopropyl-6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209152Notes

Reaction equation

HRID 2209152 reaction equation
Br[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][NH:14][C:13](=[O:16])[CH2:12]2)[CH3:10])[C:5]2[N:17]([CH:20]3[CH2:22][CH2:21]3)[CH:18]=[N:19][C:4]=2[CH:3]=1.[O:23]1[CH2:28][CH2:27][O:26][C:25]2[CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=[CH:32][C:24]1=2.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>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.O.CCOC(C)=O>[CH:20]1([N:17]2[C:5]3[C:6]([O:8][C@@H:9]([C@H:11]4[CH2:15][NH:14][C:13](=[O:16])[CH2:12]4)[CH3:10])=[N:7][C:2]([C:30]4[CH:31]=[CH:32][C:24]5[O:23][CH2:28][CH2:27][O:26][C:25]=5[CH:29]=4)=[CH:3][C:4]=3[N:19]=[CH:18]2)[CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27605922-(2,3-Dihydro-1,4-benzodioxin-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 117843105(R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-on

Product 1

HCID 117842790(R)-4-((R)-1-((3-cyclopropyl-6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

To a 25 ml 3-neck flask with condenser and magnetic stir bar was added (R)-4-((R)-1-((6-bromo-3-cyclopropyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-on (100 mg, 0.27 mmol), 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (90 mg, 0.34 mmol) and Pd(PPh3)4 (32 mg, 0.027 mmol) then evacuated and filled with N2 3×. Added 2 mL DME and 2N sodium carbonate (0.41 ml, 0.82 mmol) via syringe and heated in a 105° C. oil bath for ˜2 hrs at which time LC-MS indicated a complete reaction Let cool, added EtOAc and water, separated, washed with brine, dried over Na2SO4, filtered and concentrated. Purified by chromatography: ISCO 50 g C18 reverse phase 0-30% water/acetonitrile/0.1% TFA. Partially concentrated under reduced pressure added EtOAc and sat.aq.bicarb, separated, washed with brine, dried over Na2SO4, filtered and concentrated to give a white solid.

Workup

  1. customthen evacuated
  2. additionfilled with N2 3×
  3. customa complete reaction
  4. temperatureLet cool
  5. customseparated
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurified by chromatography
  11. concentrationPartially concentrated under reduced pressure
  12. additionadded EtOAc and sat.aq.bicarb
  13. customseparated
  14. washwashed with brine
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customto give a white solid

Sources & evidence

ORD record
ord-41ddb64ce52945009689a1fa9bb7af2e
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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