Sodium hydride → 6-[2-(Pyridin-4-yloxy)-ethoxy]-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl oxime

HRID 1853359Notes

Reaction equation

HRID 1853359 reaction equation
[H-].[Na+].[C:3]([O:7][N:8]=[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=2)[O:12][C:11]([C:20]2[N:25]=[CH:24][N:23]3[CH:26]=[CH:27][CH:28]=[C:22]3[CH:21]=2)=[CH:10]1)([CH3:6])([CH3:5])[CH3:4].Cl[CH2:30][CH2:31][O:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1.C1OCCOCCOCCOCCOC1>CN1C(=O)CCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>[C:3]([O:7][N:8]=[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH2:30][CH2:31][O:32][C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)[CH:17]=2)[O:12][C:11]([C:20]2[N:25]=[CH:24][N:23]3[CH:26]=[CH:27][CH:28]=[C:22]3[CH:21]=2)=[CH:10]1)([CH3:6])([CH3:4])[CH3:5]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 226249214-(2-Chloroethoxy)pyridineHCID 866730736-Hydroxy-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl-oxime

Product 1

HCID 866731206-[2-(Pyridin-4-yloxy)-ethoxy]-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl oximeYield 42%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent3×HCID 25517Ammonium ChlorideSolvent

Procedure

To a mixture of sodium hydride 60% in oil (11.5 mg, 0.28 mmol) in NMP (0.5 ml) was added at 0° C. a solution of 6-hydroxy-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl-oxime (example 81A) (100 mg, 0.28 mmol) in NMP (0.5 ml). After 1 hour at room temperature, a solution of 4-(2-Chloro-ethoxy)-pyridine (103 mg, 042 mmol), tetrabutyl ammonium iodide (53 mg, 0.14 mmol), 15-crown-5 (63 mg, 0.28 mmol) in NMP (0.5 ml) was added at 0° C. After stirring at room temperature for 24 hours, the reaction mixture was diluted with a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layers were washed with a saturated solution of ammonium chloride, water, brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography over silica gel (gradient cyclohexane/ethyl acetate: 0-70%) to yield the title compound (54 mg, 42%) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layers were washed with a saturated solution of ammonium chloride, water, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography over silica gel (gradient cyclohexane/ethyl acetate: 0-70%)

Sources & evidence

ORD record
ord-eb87c7a7e2ea43ddadb2f519dd9b9527
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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