Ethyl Acetate → HCID 59425449, compound

HRID 502216Notes

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) is stirred at ambient temperature for 12 hours, then heated to 80° C. for an additional 24 hours. The solution is cooled and poured into 50 mL of ethyl acetate. This is washed with water and saturated brine (50 mL each), then dried over anhydrous magnesium sulfate, filtered and evaporated. The residual material is 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 is cooled
washThis is washed with water and saturated brine (50 mL each)
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
customevaporated
customThe residual material is separated by flash chromatography (eluting 2/1 ethyl acetate/hexane on silica gel 60)

Sources & evidence

ORD record: ord-800536d87b274e9d9256a43ed5ac7c0a
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772271B2

Reaction notes

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