Pyridine → HCID 86711397, compound

HRID 926328Notes

Reaction equation

HRID 926328 reaction equation
[CH2:1]=[C:2]([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)[CH3:3].O=P(Cl)(Cl)Cl.[CH3:26][O:27][C@@H:28]([C:30]1[N:31]=[CH:32][NH:33][CH:34]=1)[CH3:29].N1C=CC=CC=1>ClCCCl.C(Cl)Cl>[CH3:26][O:27][C@@H:28]([C:30]1[N:31]=[CH:32][N:33]([C:15]2[CH:14]=[C:9]3[C:10]4[C:5]([CH2:6][CH2:7][N:8]3[C:18](=[O:19])[CH2:17][N:16]=2)=[C:4]([C:2]([CH3:3])=[CH2:1])[CH:13]=[CH:12][CH:11]=4)[CH:34]=1)[CH3:29]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 86711396HCID 86711396, compoundHCID 178496733HCID 178496733, compound

Product 1

HCID 86711397HCID 86711397, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Example 118. A solution of 9-(prop-1-en-2-yl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (275 mg, 1.03 mmol) in DCE (20 mL) was treated with POCl3 (0.29 mL, 3.07 mmol) and the mixture was heated to 100° 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 (R)-4-(1-methoxyethyl)-1H-imidazole (200 mg, 1.59 mmol) and pyridine (0.17 mL, 2.05 mmol) were 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: 4-Ethylpyridine 5 μm, 250×30 mm, 60 A, Princeton; eluent: 6% MeOH/CO2 for 1 min, then from 6% MeOH/CO2 to 11% MeOH/CO2 in 6 min; then from 11% MeOH/CO2 to 50% MeOH/CO2 in 1 min; flow 100 mL/min; UV detection at 220 nm) gave the title compound (60 mg). UPLC-MS: MS 377.2 (M+H+); UPLC rt 1.02 min. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.35 (d, J=5.87 Hz, 3 H); 2.01 (s, 3 H); 2.90 (t, J=5.87 Hz, 2 H); 3.14 (s, 3 H); 3.75 (t, J=6.06 Hz, 2 H); 4.16-4.33 (m, 3 H); 4.85 (s, 1 H); 5.29 (s, 1 H); 7.12 (s, 1 H); 7.27-7.40 (m, 2 H); 7.57 (s, 1 H); 7.90 (d, J=7.82 Hz, 1 H); 8.18 (s, 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
  14. waitfrom 6% MeOH/CO2 to 11% MeOH/CO2 in 6 min
  15. waitthen from 11% MeOH/CO2 to 50% MeOH/CO2 in 1 min

Sources & evidence

ORD record
ord-5a5d826ab1b1405dad9cd66d48bdebaf
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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