18-Crown-6 → 4-(2-((Quinazolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

HRID 1772639Notes

Reaction equation

HRID 1772639 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.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].Cl[C:43]1[N:52]=[CH:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[N:44]=1>C1COCC1.C(Cl)Cl.[NH4+].[Cl-].C(OCC)C>[N:44]1[C:45]2[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:51]=[N:52][C:43]=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

9

Reactant 4

HCID 2855718-Crown-6HCID 740542-ChloroquinazolineHCID 23665647Potassium tert-butoxideHCID 117728187(8-Morpholinoimidazo[1,2-a]pyrazin-2-yl)methanol

Product 1

HCID 1177279694-(2-((Quinazolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-8-yl)morpholine

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of compound 1d (600.0 mg, 2.50 mmol) in THF (10 mL) was added 18-crown-6 (677 mg, 2.60 mmol), followed by potassium tert-butoxide (575 mg, 5.12 mmol). The reaction mixture was stirred at rt for 10 min and treated with 2-chloroquinazoline (632 mg, 3.84 mmol). The resulting mixture was stirred for 10 more min at rt and then at 120° C. for 1 h. The reaction mixture was then allowed to cool to rt, diluted with 20 mL of DCM and 20 mL of saturated aqueous NH4Cl. The organic layer was separated, dried over Na2SO4, and concentrated. The residue obtained was purified by flash column chromatography on silica gel (1:0-4:1 DCM/EtOAc) to obtain a white solid. The solid was then suspended in diethyl ether (50 mL) and sonicated for 5 min, before collecting by filtration to yield compound 22a. Mass Spectrum (LCMS, ESI pos.) Calcd. For C19H18N6O2: 363.1 (M+H). Found 363.1.

Workup

  1. stirringThe resulting mixture was stirred for 10 more min at rt
  2. waitat 120° C. for 1 h
  3. temperatureto cool to rt
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customwas purified by flash column chromatography on silica gel (1:0-4:1 DCM/EtOAc)
  9. customto obtain a white solid
  10. customsonicated for 5 min
  11. filtrationbefore collecting by filtration

Sources & evidence

ORD record
ord-18def3e28a934a278528aafd74be37e7
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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