Phosphorus oxychloride → HCID 89980667, compound

HRID 926333Notes

Reaction equation

HRID 926333 reaction equation
C([C:5]1[C:6](=O)[NH:7][CH2:8][C:9](=[O:20])[N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=12)(C)(C)C.O=P(Cl)(Cl)Cl.[CH3:27][O:28][CH2:29][C:30]1[N:31]=[CH:32][NH:33][CH:34]=1>ClCCCl.C(Cl)Cl>[C:12]([C:16]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:17]=1[CH2:18][CH2:19][N:10]1[C:9](=[O:20])[CH2:8][N:7]=[C:6]([N:33]3[CH:34]=[C:30]([CH2:29][O:28][CH3:27])[N:31]=[CH:32]3)[CH:5]=[C:11]12)([CH3:17])([CH3:13])[CH3:11]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 131735016HCID 131735016, compoundHCID 178494610HCID 178494610, compound

Product 1

HCID 89980667HCID 89980667, compoundYield 33.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
110 °C

Procedure

Example 125. A solution of -(tert-butyl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (370 mg, 1.30 mmol) in DCE (20 mL) was treated with POCl3 (0.24 mL, 2.60 mmol) and the mixture was heated to 110° C. for 1 h. The mixture was then allowed to cool to RT, diluted with DCM and washed with H2O. The org. phase was then dried over Na2SO4, filtered and concentrated in vacuo. The residue obtained was taken up in DCE (20 mL) and 4-(methoxymethyl)-1H-imidazole (438 mg, 3.90 mmol) was then added. The mixture was heated to 110° C. for 1 h, and then allowed to cool to RT, diluted with DCM and washed with H2O. The org. layer was then dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 85:15) and SFC (column: PPU 5 μm, 250×30 mm, 60 A, Princeton; eluent: isocratic 5% MeOH/CO2 for 11 min; flow 100 mL/min; UV detection at 220 nm) gave the title compound (83 mg). UPLC-MS: MS 379.2 (M+H+); UPLC rt 1.04 min. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.38 (s, 9 H); 3.10-3.20 (m, 2 H); 3.22 (br s, 3 H); 3.63 (m, 2 H); 4.25 (m, 4 H); 6.86 (d, J=1.96 Hz, 1 H); 7.31 (s, 1 H); 7.49 (d, J=8.21 Hz, 1 H); 7.54-7.69 (m, 2 H); 8.17 (d, J=1.56 Hz, 1 H).

Workup

  1. temperatureto cool to RT
  2. washwashed with H2O
  3. dry with materialphase was then dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. temperatureThe mixture was heated to 110° C. for 1 h
  8. temperatureto cool to RT
  9. washwashed with H2O
  10. dry with materiallayer was then dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 85:15) and SFC (column: PPU 5 μm, 250×30 mm, 60 A, Princeton; eluent: isocratic 5% MeOH/CO2 for 11 min; flow 100 mL/min; UV detection at 220 nm)

Sources & evidence

ORD record
ord-87b9e65084c144c293cdbda384b48eb3
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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