Phosphorus oxychloride → N-(4-chloro-9H-pyrimido[4,5-b]indol-2-yl)-2,2-dimethylpropanamide
Reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([NH:5][C:6]1[NH:7][C:8](=O)[C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[N:18]=1)=[O:4].P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:8]1[C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[N:18]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:21])([CH3:20])[CH3:1])[N:7]=1Participants
Procedure
In a 50 mL R.B.F. was placed 5 (56 mg, 0.17 mmol) and phosphoryl trichloride (15 mL). The mixture was stirred and heated at reflux for 4 hours. The phosphoryl trichloride was evaporated under reduced pressure using a vacuum aspirator. The resulting residue was cooled in an ice and water mixture, and neutralized with ammonium hydroxide solution to yield a precipitate that was filtered and dried over P2O5. The filterate was extracted with chloroform and dried over sodium sulfate. The dry precipitate and filterate were combined and evaporated to provide 35 mg of 6 as a brown solid in 59% yield. Compound 6 was used without further purification for the subsequent step. TLC Rf 0.65 (chloroform-methanol 10:1); mp 234° C.; 1H NMR (DMSO-d6) δ 1.24 (s, 9H, C(CH3)3), 7.36-8.17 (m, 4H, Ar—H), 10.25 (s, 1H, 2-NH, exch), 12.55 (s, 1H, 9-NH, exch). Anal. Calculated (C15H15ClN4O. 0.15H2O): C, 58.98; H, 5.04; N, 18.34; Cl, 11.60. Found: C, 59.00; H, 5.09; N, 17.97; Cl, 11.83.
Workup
- temperatureheated
- temperatureat reflux for 4 hours
- customThe phosphoryl trichloride was evaporated under reduced pressure
- temperatureThe resulting residue was cooled in an ice and water mixture
- customto yield a precipitate that
- filtrationwas filtered
- dry with materialdried over P2O5
- extractionThe filterate was extracted with chloroform
- dry with materialdried over sodium sulfate
- customevaporated
Sources & evidence
- ORD record
- ord-1fcc159efe724945825c773a2402014d
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08309564B2
Reaction notes
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