p-Toluenesulfonic acid → HCID 86721325, compound
Reaction equation
[Cl:1][C:2]1[C:3](O)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH:17]3[CH2:19][CH2:18]3)=[C:13]([CH:16]=2)[C:14]#[N:15])=[N:6][CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O=P(Cl)(Cl)[Cl:34]>>[Cl:34][C:3]1[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH:17]3[CH2:19][CH2:18]3)=[C:13]([CH:16]=2)[C:14]#[N:15])[N:4]=1Participants
Procedure
5-(5-chloro-4-hydroxypyrimidin-2-ylamino)-2-cyclopropylbenzonitrile, containing 1.2 equivalents of p-toluenesulfonic acid (1.00 g, 2.03 mmol) was weighed out and added to a flask with a magnetic stir bar. This was suspended in 11 mL POCl3 and the reaction was heated at reflux for 3 hours. This was evaporated, then quenched with cold 10% aqueous Na2CO3. The mixture was extracted 4 times with ethyl acetate and the combined organic layer was dried over sodium sulfate. This was filtered, concentrated onto a plug of silica, and purified by column chromatography. Pure product was concentrated and dried on the high vacuum to give 493 mg of 5-(4,5-dichloropyrimidin-2-ylamino)-2-cyclopropylbenzonitrile (80% yield, accounting for the mass of p-toluenesulfonic acid present in the starting material).
Workup
- additionadded to a flask with a magnetic stir bar
- temperaturethe reaction was heated
- temperatureat reflux for 3 hours
- customThis was evaporated
- customquenched with cold 10% aqueous Na2CO3
- extractionThe mixture was extracted 4 times with ethyl acetate
- dry with materialthe combined organic layer was dried over sodium sulfate
- filtrationThis was filtered
- concentrationconcentrated onto a plug of silica
- custompurified by column chromatography
- concentrationPure product was concentrated
- customdried on the high vacuum
Sources & evidence
- ORD record
- ord-8e278dfd62b44c2489f7eb17d1b2436f
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09062068B2
Reaction notes
Loading…