Ethyl Acetate → diethyl [4-(3-cyano-6-ethoxy-1-ethyl-1H-indol-2-yl)-phenyl]-phosphoramidate

HRID 907195Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:22][CH3:23])[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH3:21])[CH:11]=3)=[CH:4][CH:3]=1.[P:24](Cl)([O:29][CH2:30][CH3:31])([O:26][CH2:27][CH3:28])=[O:25].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>O1CCOCC1>[C:17]([C:16]1[C:15]2[C:10](=[CH:11][C:12]([O:19][CH2:20][CH3:21])=[CH:13][CH:14]=2)[N:9]([CH2:22][CH3:23])[C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][P:24](=[O:25])([O:29][CH2:30][CH3:31])[O:26][CH2:27][CH3:28])=[CH:7][CH:6]=1)#[N:18]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 2-(4-aminophenyl)-6-ethoxy-1-ethyl-1H-indole-3-carbonitrile (148 mg, 0.484 mmol), diethyl chlorophosphate (0.086 mL, 0.58 mmol) and diisopropylethylamine (0.10 mL, 0.57 mmol) in 1,4-dioxane (5 mL) was stirred at ambient temperature for 12 hours, then heated to 80° C. for an additional 24 hours. The solution was cooled and poured into 50 mL of ethyl acetate. This was washed with water and saturated brine (50 mL each), then dried over anhydrous magnesium sulfate, filtered and evaporated. The residual material was separated by flash chromatography (eluting 2/1 ethyl acetate/hexane on silica gel 60) to afford diethyl [4-(3-cyano-6-ethoxy-1-ethyl-1H-indol-2-yl)-phenyl]-phosphoramidate (108 mg, 0.245 mmol, 51%) as a white powder after evaporation.

Workup

temperatureThe solution was cooled
washThis was washed with water and saturated brine (50 mL each)
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
customevaporated
customThe residual material was separated by flash chromatography (eluting 2/1 ethyl acetate/hexane on silica gel 60)

Sources & evidence

ORD record: ord-e1d8cc8c1bd64062b18274c1ea2a0cbe
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013006B2

Reaction notes

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