2-Chloroquinoline → 4-(2-((Quinolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

HRID 1772658Notes

Reaction equation

HRID 1772658 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:13]=[C:14]([CH2:16][OH:17])[N:15]=3)[CH:10]=[CH:11][N:12]=2)[CH2:3][CH2:2]1.[H-].[Na+].Cl[C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1>C1COCC1>[N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:29]=[CH:30][C:21]=1[O:17][CH2:16][C:14]1[N:15]=[C:8]2[C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[N:12][CH:11]=[CH:10][N:9]2[CH:13]=1

Participants

5

Reactant 3

HCID 119282-ChloroquinolineHCID 24758Sodium hydrideHCID 117728187(8-Morpholinoimidazo[1,2-a]pyrazin-2-yl)methanol

Product 1

HCID 1177283094-(2-((Quinolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of compound 1d (5.0 g, 21 mmol) and NaH (2.5 g, 64 mmol) in anhydrous THF (300 mL) was stirred at rt for 10 min. 2-Chloroquinoline (4.2 g, 25 mmol) was then added and the mixture was heated to 70° C. for 5 h. The reaction was quenched with brine (300 mL) and extracted with EtOAc (2×500 mL). The organic layer was washed with brine (300 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue obtained was recrystallized with hot EtOAc-hexanes to give compound 31a. Mass Spectrum (LCMS, ESI pos.): Calcd. for C20H19N5O2: 362.1 (M+H). found: 362.2.

Workup

  1. temperaturethe mixture was heated to 70° C. for 5 h
  2. customThe reaction was quenched with brine (300 mL)
  3. extractionextracted with EtOAc (2×500 mL)
  4. washThe organic layer was washed with brine (300 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customwas recrystallized with hot EtOAc-hexanes

Sources & evidence

ORD record
ord-1dbcacfede124fe3850c17500ba6a441
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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