Sodium ethoxide → 2'-(3-(4-(4-chlorophenyl)piperazin-1-yl)propyl)-7',8'-dihydro-3'H-spiro[cyclopropane-1,6'-quinazolin]-4'(5'H)-one

HRID 2200349Notes

Reaction equation

HRID 2200349 reaction equation
[Na].[O-]CC.[Na+].O=[C:7]1[CH2:14][CH2:13][C:10]2([CH2:12][CH2:11]2)[CH2:9][CH:8]1[C:15]([O:17]CC)=O.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][C:36](=[NH:38])[NH2:37])[CH2:29][CH2:28]2)=[CH:23][CH:22]=1>O.C(O)C>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([N:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][C:36]3[NH:38][C:15](=[O:17])[C:8]4[CH2:9][C:10]5([CH2:11][CH2:12]5)[CH2:13][CH2:14][C:7]=4[N:37]=3)[CH2:29][CH2:28]2)=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 24209564Ethyl 6-oxospiro[2.5]octane-5-carboxylateHCID 433181844-(4-(4-Chlorophenyl)piperazin-1-yl)butanimidamide

Product 1

HCID 1362747952'-(3-(4-(4-chlorophenyl)piperazin-1-yl)propyl)-7',8'-dihydro-3'H-spiro[cyclopropane-1,6'-quinazolin]-4'(5'H)-oneYield 5.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Sodium (0.094 g, 4.08 mmol) was added to ethanol (15 ml) under stirring condition at room temperature. The resulting mixture was stirred for 30 min. To this freshly prepared clear solution of sodium ethoxide, were added ethyl 6-oxospiro[2.5]octane-5-carboxylate (0.4 g, 2.03 mmol) and 4-(4-(4-chlorophenyl) piperazin-1-yl)butanimidamide (0.343 g, 1.223 mmol) and the reaction mixture was heated at 85° C. for 18 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain crude residue which was dissolved with water (15 ml). Aqueous layer was extracted with ethylacetate (2×30 ml). The combined organic layer was dried over sodium sulphate, filtered and solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh) using 3-4% methanol in dichloromethane as eluent to obtain title compound (0.030 g, 4% yield).

Workup

  1. stirringThe resulting mixture was stirred for 30 min
  2. temperaturethe reaction mixture was heated at 85° C. for 18 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customto obtain crude residue which
  6. extractionAqueous layer was extracted with ethylacetate (2×30 ml)
  7. dry with materialThe combined organic layer was dried over sodium sulphate
  8. filtrationfiltered
  9. customsolvent was removed under reduced pressure
  10. customto obtain a crude product which
  11. customwas purified by flash chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-fdcd9f8d0e0740e8a9bd794db78ffaa3
Source dataset
uspto-grants-2016_06
Patent number
US09359367B2

Reaction notes

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