N,N-Dimethylaniline → HCID 86696590, compound
Reaction equation
O[C:2]1[N:7]2[N:8]=[C:9]3[C:14]([CH:13]=[CH:12][CH:11]=[CH:10]3)=[C:6]2[N:5]=[C:4]([CH3:15])[C:3]=1[CH2:16][C:17]([O:19][CH3:20])=[O:18].CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:32])=O>>[Cl:32][C:2]1[N:7]2[N:8]=[C:9]3[C:14]([CH:13]=[CH:12][CH:11]=[CH:10]3)=[C:6]2[N:5]=[C:4]([CH3:15])[C:3]=1[CH2:16][C:17]([O:19][CH3:20])=[O:18]Participants
Conditions
- Temperature
- 60 °C
Procedure
The methyl 2-(4-hydroxy-2-methylpyrimido[1,2-b]indazol-3-yl)acetate (1.34 g; 4.94 mmol) was suspended in phosphorus oxychloride (5.1 mL) and dimethylaniline (0.96 mL) was added under nitrogen atmosphere. The well-stirred reaction mixture was heated at 60° C. for 3 days. Phosphorus oxychloride in excess was removed under reduced pressure and the remaining oil was placed in an ice-bath. A cold saturated sodium hydrogenocarbonate solution was carefully added until neutralization. The aqueous layer was extracted with ethyl acetate, the organics were combined, dried over sodium sulfate, concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (1-20%) in dichloromethane furnished 0.659 g (46%) of methyl 2-(4-chloro-2-methylpyrimido[1,2-b]indazol-3-yl)acetate as a light yellow solid. ESI/APCI(+): 290-292 (M+H).
Workup
- customThe well-stirred reaction mixture
- customPhosphorus oxychloride in excess was removed under reduced pressure
- customthe remaining oil was placed in an ice-bath
- additionA cold saturated sodium hydrogenocarbonate solution was carefully added until neutralization
- extractionThe aqueous layer was extracted with ethyl acetate
- dry with materialdried over sodium sulfate
- concentrationconcentrated under reduced pressure
- customPurification by flash chromatography on silica gel using a gradient of ethyl acetate (1-20%) in dichloromethane
Sources & evidence
- ORD record
- ord-9671f59e8e60438caec435ad5a92ad7e
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09132129B2
Reaction notes
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