Triethylamine → HCID 19925648, compound

HRID 1647510Notes

Reaction equation

HRID 1647510 reaction equation
CNC1C=[CH:7][C:6]([S:9][C:10]2[CH:11]=[C:12]([C:16]3([O:22][CH3:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH:13]=[CH:14][CH:15]=2)=[CH:5][CH:4]=1.[CH2:24]([N:26]([CH2:29]C)[CH2:27][CH3:28])C.ClC(Cl)([O:34]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(Cl)Cl.C(OCC)(=O)C>[CH3:43][N:44]1[CH2:49][CH2:48][N:47]([C:29]([N:26]([C:27]2[CH:28]=[CH:7][C:6]([S:9][C:10]3[CH:11]=[C:12]([C:16]4([O:22][CH3:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH:13]=[CH:14][CH:15]=3)=[CH:5][CH:4]=2)[CH3:24])=[O:34])[CH2:46][CH2:45]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 94429TriphosgeneHCID 19925606HCID 19925606, compound

Product 1

HCID 19925648HCID 19925648, compoundYield 133.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a methylene chloride (16 mL) solution of 4-{3-[4-(N-methylamino)phenylthio]phenyl}-4-methoxytetrahydropyran (517 mg, 1.57 mmol; prepared in step 8 of Example 29) was added triethylamine (0.22 mL, 1.57 mmol) and triphosgene (23.3 mg, 0.79 mmol) in methylenechloride (5 mL). The resulting solution was stirred at ambient temperature for 0.5 h, N-methylpiperazine (0.70 mL, 6.3 mmol) was added, and the mixture was stirred for another hour at ambient temperature. The reaction mixture was partitioned between ethyl acetate and 10% aqueous HCl. The layers were separated and the organic layer was washed (1×, saturated sodium bicarbonate; 2×, water; 2×, brine), dried (MgSO4), filtered and concentrated under vacuum. The resulting residue was chromatographed over silica gel (5% ethanol:methylene chloride+1% ammonium hydroxide) to give a light yellow oil. The oil was dissolved in ethyl acetate, treated with decolorizing carbon, and filtered through a celite pad. Removal of the volatiles under vacuum and drying the residue under high vacuum provided the title compound as a colorless oil (482 mg, 67%). 1H NMR (300 MHz, CDCl3) δ7.48 (1H, m), 7.15-7.38 (5H, m), 7.04 (2H, d, J=9 Hz), 3.77-3.89 (4H; m), 3.2-3.28 (4H; m), 3.24 (3H, s), 2.97 (3H, s), 2.20-2.28 (4H; m), 2.24 (3H; s), 1.88-2.04 (4H, m). MS m/e (M+H)+ =456; Analysis calc'd for C25H33N3O3S: C, 65.91; H, 7.30; N, 9.22. Found: C, 65.86; H, 7.25; N, 9.22.

Workup

  1. stirringthe mixture was stirred for another hour at ambient temperature
  2. customThe reaction mixture was partitioned between ethyl acetate and 10% aqueous HCl
  3. customThe layers were separated
  4. washthe organic layer was washed (1×, saturated sodium bicarbonate; 2×, water; 2×, brine)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe resulting residue was chromatographed over silica gel (5% ethanol:methylene chloride+1% ammonium hydroxide)
  9. customto give a light yellow oil
  10. additiontreated with decolorizing carbon
  11. filtrationfiltered through a celite pad
  12. customRemoval of the volatiles under vacuum
  13. customdrying the residue under high vacuum

Sources & evidence

ORD record
ord-abf40a95b3b3459abe922765b2bb8fe5
Source dataset
uspto-grants-1995_07
Patent number
US05432194

Reaction notes

Loading…