Triethylamine → 5,7-Dichloro-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][NH:8][C:7](=O)[C:6]=2[CH:15]=1.CCN(CC)CC.O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:7]1[C:6]2[CH:15]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][N:8]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
As illustrated in the scheme above, 7-chloro-3,4-dihydro-1-methyl-1H-1,4-benzodiazepine-2,5-dione (5.00 g, 22.3 mmol) was suspended in POCl3 (100 mL) and heated at 100° C. for 30 min. The reaction was cooled and concentrated in vacuo. Traces of POCl3 were removed by adding toluene and concentrating the mixture in vacuo (2×). The residue was dissolved in CH2Cl2, the solution was cooled to 0° C., and Et3N (6.8 mL, 48.8 mmol) was added dropwise. The mixture was stirred for 1 h and allowed to slowly warm to room temperature, and was then concentrated in vacuo once again. The residue was purified by silica gel column chromatography (5:1 CH2Cl2:EtOAc+0.5% Et3N) to provide the title compound as an orange solid (4.68 g, 86%). 1H-NMR (CDCl3): δ 7.79 (d, J=2.5 Hz, 1H), 7.55 (dd, J=2.4 Hz, J=8.9 Hz, 1H), 7.23 (d, J=8.8 Hz, 1H), 4.67 (br s, 1H), 3.72 (br s, 1H), 3.39 (s, 3H). MS (ESI) (M+H)+=243.
Workup
- temperatureThe reaction was cooled
- concentrationconcentrated in vacuo
- customTraces of POCl3 were removed
- additionby adding toluene
- concentrationconcentrating the mixture in vacuo (2×)
- dissolutionThe residue was dissolved in CH2Cl2
- temperaturethe solution was cooled to 0° C.
- temperatureto slowly warm to room temperature
- concentrationwas then concentrated in vacuo once again
- customThe residue was purified by silica gel column chromatography (5:1 CH2Cl2:EtOAc+0.5% Et3N)
Sources & evidence
- ORD record
- ord-5cd416555210482a9d4f5e0adbde93dd
- Source dataset
- uspto-grants-2008_05
- Patent number
- US07375101B2
Reaction notes
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