Sodium hydride → 6,7-Dichloro-2,3-dimethoxy-5-{4-[3-(4-morpholinyl)propyl]pyrazol-1-ylmethyl}quinoxaline

HRID 1957112Notes

Reaction equation

Cl.Cl.[N:3]1([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[N:14][NH:15][CH:16]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[H-].[Na+].Br[CH2:20][C:21]1[C:30]([Cl:31])=[C:29]([Cl:32])[CH:28]=[C:27]2[C:22]=1[N:23]=[C:24]([O:35][CH3:36])[C:25]([O:33][CH3:34])=[N:26]2.[Cl-].[NH4+]>O>[Cl:31][C:30]1[C:21]([CH2:20][N:15]2[CH:16]=[C:12]([CH2:11][CH2:10][CH2:9][N:3]3[CH2:8][CH2:7][O:6][CH2:5][CH2:4]3)[CH:13]=[N:14]2)=[C:22]2[C:27](=[CH:28][C:29]=1[Cl:32])[N:26]=[C:25]([O:33][CH3:34])[C:24]([O:35][CH3:36])=[N:23]2

Participants

Conditions

Temperature: -40 °C

Procedure

4-[3-(4-Morpholinyl)propyl]pyrazole dihydrochloride (268 mg, 1 mmol) was added to a stirred suspension of sodium hydride (120 mg, 80% oil dispersion, 4 mmol) at 0° C. under nitrogen. After 30 minutes, the mixture was cooled to -40° C. and 5-bromomethyl-6,7-dichloro-2,3-dimethoxyquinoxaline (Preparation 1, 235 mg, 0.67 mmol) was added. The mixture was allowed to warm to -20° C. over 1 hour and saturated aqueous ammonium chloride (20 mL) was added. The mixure was diluted with water (100 mL) and extracted with ethyl acetate (2×100 mL). The extracts were washed with water, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with dichloromethane, then ethyl acetate then finally ethyl acetate:methanol:triethylamine (100:3:1) to give 6,7-dichloro-2,3-dimethoxy-5-{4-[3-(4-morpholinyl)propyl]pyrazol-1-ylmethyl}quinoxaline (278 mg, 89%) as a colourless gum.

Workup

temperatureto warm to -20° C. over 1 hour
extractionextracted with ethyl acetate (2×100 mL)
washThe extracts were washed with water
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customThe residue was purified by flash chromatography
washeluting with dichloromethane

Sources & evidence

ORD record: ord-42b4e540b7a34c82a29c56ee14be9539
Source dataset: uspto-grants-1998_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05783572

Reaction notes

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