5-Bromo-2-chloropyrimidine → (1-(5-Bromopyrimidin-2-yl)-3-(methylthio)-1H-indol-6-yl)(morpholino)methanone

HRID 630441Notes

Reaction equation

CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:9]=[N:10][C:11](Cl)=[N:12][CH:13]=1.[CH3:15][S:16][C:17]1[C:25]2[C:20](=[CH:21][C:22]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[CH:23][CH:24]=2)[NH:19][CH:18]=1>CN(C=O)C.C(OCC)(=O)C>[Br:7][C:8]1[CH:9]=[N:10][C:11]([N:19]2[C:20]3[C:25](=[CH:24][CH:23]=[C:22]([C:26]([N:28]4[CH2:29][CH2:30][O:31][CH2:32][CH2:33]4)=[O:27])[CH:21]=3)[C:17]([S:16][CH3:15])=[CH:18]2)=[N:12][CH:13]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Potassium tert-butoxide (9.75 g, 86.95 mmol, 1.5 eq) and 5-bromo-2-chloropyrimidine (11.21 g, 57.97 mmol, 1.0 eq) were added to (3-(methylthio)-1H-indol-6-yl)(morpholino)methanone (16.0 g, 57.97 mmol, 1.0 eq) in DMF (100 mL). The mixture was stirred at 120° C. for 16 h, then cooled to room temperature, diluted with ethyl acetate (100 mL), and filtered through a pad of celite. The filtrate was washed with water (2×100 mL) and brine (50 mL), and dried over sodium sulphate. The solvents were distilled off and the residue was purified by silica gel column chromatography [100-200 mesh; ethyl acetate/petrolether=1:1]. Yield: 8.0 g (32% over two steps).

Workup

temperaturecooled to room temperature
filtrationfiltered through a pad of celite
washThe filtrate was washed with water (2×100 mL) and brine (50 mL)
dry with materialdried over sodium sulphate
distillationThe solvents were distilled off
customthe residue was purified by silica gel column chromatography [100-200 mesh; ethyl acetate/petrolether=1:1]

Sources & evidence

ORD record: ord-b864346925db4c8393abfa8744851229
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315490B2

Reaction notes

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