Sodium Carbonate → Tert-butyl cyclopropyl(3-formyl-6-(3-(morpholinomethyl)phenyl)imidazo[1,2-a]pyrazin-8-yl)carbamate

HRID 624761Notes

Reaction equation

HRID 624761 reaction equation
Br[C:2]1[N:3]=[C:4]([N:13]([CH:21]2[CH2:23][CH2:22]2)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2[N:6]([C:8]([CH:11]=[O:12])=[CH:9][N:10]=2)[CH:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([CH:42]=[CH:43][CH:44]=2)[CH2:35][N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[CH:21]1([N:13]([C:4]2[C:5]3[N:6]([C:8]([CH:11]=[O:12])=[CH:9][N:10]=3)[CH:7]=[C:2]([C:43]3[CH:44]=[CH:32][CH:33]=[C:34]([CH2:35][N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH:42]=3)[N:3]=2)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27955784-[3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]morpholineHCID 86714607Tert-butyl 6-bromo-3-formylimidazo[1,2-a]pyrazine-8-yl(cyclopropyl)carbamate

Product 1

HCID 86714608Tert-butyl cyclopropyl(3-formyl-6-(3-(morpholinomethyl)phenyl)imidazo[1,2-a]pyrazin-8-yl)carbamateYield 48.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Tert-butyl 6-bromo-3-formylimidazo[1,2-a]pyrazine-8-yl(cyclopropyl)carbamate (100 mg, 0.26 mmol), 4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]morpholine (118 mg, 0.39 mmol), 3M Na2CO3 (1.3 mL, 2.60 mmol) and DME (3.5 mL) were combined. The solution was degassed with a stream of N2 for 10 min. Pd(PPh3)4 was added and the solution was refluxed for 2 h. The solution was partitioned between dichloromethane (25 mL) and water (25 mL). The aqueous layer was further extracted with dichloromethane (2×25 mL). The organics were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified via preparative TLC (5% MeOH/dichloromethane) to afford tert-butyl cyclopropyl(3-formyl-6-(3-(morpholinomethyl)phenyl)imidazo[1,2-a]pyrazin-8-yl)carbamate (60 mg, 48%). LCMS (ES): >95% pure, m/z 478 [M+1]+.

Workup

  1. customThe solution was degassed with a stream of N2 for 10 min
  2. additionPd(PPh3)4 was added
  3. temperaturethe solution was refluxed for 2 h
  4. customThe solution was partitioned between dichloromethane (25 mL) and water (25 mL)
  5. extractionThe aqueous layer was further extracted with dichloromethane (2×25 mL)
  6. washThe organics were washed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified via preparative TLC (5% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-2d6f2cf4231947ba8f033bf490fc8ece
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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