Ethyl isocyanate → 1-[3-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-3-ethyl urea

HRID 907136Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[N:11]([CH2:23][CH3:24])[C:12]3[C:17]([C:18]=2[C:19]#[N:20])=[CH:16][CH:15]=[C:14]([O:21][CH3:22])[CH:13]=3)[CH:5]=[CH:6][CH:7]=1.[CH2:25]([N:27]=[C:28]=[O:29])[CH3:26]>N1C=CC=CC=1.CCOC(C)=O>[C:19]([C:18]1[C:17]2[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][CH:16]=2)[N:11]([CH2:23][CH3:24])[C:10]=1[C:9]#[C:8][C:4]1[CH:3]=[C:2]([NH:1][C:28]([NH:27][CH2:25][CH3:26])=[O:29])[CH:7]=[CH:6][CH:5]=1)#[N:20]

Participants

Conditions

Temperature: 100 °C

Procedure

2-(3-Aminophenylethynyl)-1-ethyl-6-methoxy-1H-indole-3-carbonitrile (100 mg, 0.32 mmol), prepared as described in Example 1H, was dissolved in pyridine (670 μL). Ethyl isocyanate (62 μL, 0.75 mmol) was added. The reaction mixture was then heated at 100° C. for 2 h. The mixture was then diluted in EtOAc, and was washed with aqueous HCl, followed by brine. The organic layer was dried and concentrated. Purification by silica chromatography (4/1, CH2Cl2/EtOAc), followed by trituration with hexanes/acetone (1/1), yielded 1-[3-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-3-ethyl urea (44 mg, 36%) as a white solid.

Workup

washwas washed with aqueous HCl
customThe organic layer was dried
concentrationconcentrated
customPurification by silica chromatography (4/1, CH2Cl2/EtOAc)

Sources & evidence

ORD record: ord-a2ccdf67d77f4e03bede9e4a2a8e2cf7
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013006B2

Reaction notes

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