Phosphorus oxychloride → HCID 86711395, compound

HRID 532952Notes

Reaction equation

HRID 532952 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][N:8]1[C:18](=[O:19])[CH2:17][NH:16][C:15](=O)[CH:14]=[C:9]12)(=[O:3])[CH3:2].O=P(Cl)(Cl)Cl.[CH2:26]([C:28]1[N:29]=[CH:30][NH:31][CH:32]=1)[CH3:27].C([O-])(O)=O.[Na+]>ClCCCl.O>[C:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][N:8]1[C:18](=[O:19])[CH2:17][N:16]=[C:15]([N:31]3[CH:32]=[C:28]([CH2:26][CH3:27])[N:29]=[CH:30]3)[CH:14]=[C:9]12)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 86711378HCID 86711378, compoundHCID 178437183HCID 178437183, compound

Product 1

HCID 86711395HCID 86711395, compoundYield 128.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

115-1. A mixture of 9-acetyl-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione [example 100-1] (128 mg, 0.47 mmol) in DCE (4 mL) was treated with POCl3 (0.053 mL, 0.57 mmol) and heated to 110° C. for 1 h. The mixture was then allowed to cool to RT and then poured onto cooled H2O. The mixture was extracted with DCM and the combined org. phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue obtained was taken up in DCE (4 mL) and 4-ethyl-1H-imidazole (182 mg, 1.89 mmol) was added. The mixture was heated to 110° C. for 1 h, then allowed to cool to rt and poured onto a saturated aq. solution of NaHCO3. The mixture was extracted with DCM and the combined org. layers were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (210 mg) that was used as it is in the next step. UPLC-MS: MS 349.2 (M+H+); UPLC rt 0.71 min.

Workup

  1. temperatureto cool to RT
  2. additionpoured
  3. extractionThe mixture was extracted with DCM
  4. dry with materialphases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue obtained
  8. temperatureThe mixture was heated to 110° C. for 1 h
  9. temperatureto cool to rt
  10. extractionThe mixture was extracted with DCM
  11. dry with materiallayers were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-44b1b85e8443404ca4332bda281206c4
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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