Triethylamine → HCID 131719554, compound

HRID 743696Notes

Reaction equation

HRID 743696 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:3]=1.ClC(Cl)(O[C:19](=[O:25])OC(Cl)(Cl)Cl)Cl.C(N([CH2:32][CH3:33])CC)C.[NH2:34][CH:35]1[N:41]=[C:40](C2CCCCC2)[C:39]2[CH:48]=[CH:49][CH:50]=[CH:51][C:38]=2[N:37]([CH2:52][CH2:53][CH3:54])[C:36]1=[O:55]>O1CCCC1>[CH2:33]1[CH2:32][CH:4]([C:35]2([NH:34][C:19]([NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([N:8]4[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]4)[CH:3]=3)=[O:25])[N:41]=[CH:40][C:39]3[CH:48]=[CH:49][CH:50]=[CH:51][C:38]=3[N:37]([CH2:52][CH2:53][CH3:54])[C:36]2=[O:55])[CH2:3][CH2:2][CH2:7]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 11044766HCID 11044766, compoundHCID 115646133-(4-Methylpiperazin-1-yl)aniline

Product 1

HCID 131719554HCID 131719554, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-amino-3-(N-methyl-N'-piperazinyl) benzene (140 mg) in anhydrous tetrahydrofuran (20 ml) at 0° C., under an atmosphere of nitrogen, was added triphosgene (71 mg). After 2 min, triethylamine (260 μl) was added dropwise and the mixture stirred at 0° C. for 5 min then at room temperature for 10 min. The mixture was then cooled back to 0° C. and a solution of crude 3(R,S)-amino-5-cyclohexyl-1,3-dihydro-1-propyl-2H-1,4-benzodiazepin-2-one (150 mg) in anhydrous tetrahydrofuran (5 ml) dropwise. The mixture was stirred at 0° C. for 5 min then at room temperature for 10 min. The mixture was filtered and the filtrate evaporated in vacuo. The residue was partitioned between ethyl acetate (30 ml) and water (30 ml) and an undissolved solid filtered off. The organic phase from the filtrate was separated and the aqueous phase washed once more with ethyl acetate (10 ml). The combined organic layers were washed with brine (20 ml), dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed on silica gel using 95:5:1 dichloromethane:methanol:ammonia as the solvent. After trituration with ether the title urea (77 mg) was isolated as a white solid. Mp 255°-257° C. 1H NMR (360 MHz, D6 -DMSO) δ 0.73 (3H, t, J=7.3 Hz), 0.92 (1H, m), 1.07-1.90 (11H, m), 2.19 (3H, s), 2.39-2.42 (4H, m), 2.95 (1H, m), 3.02-3.05 (4H, m), 3.62-3.67 (1H, m), 4.16-4.22 (1H, m), 5.02 (1H, d, J=8.6 Hz), 6.49 (1H, dd, J=8 and 1.5 Hz), 6.01 (1H, d, J=8 and 1.5 z), 7.03 (1H, t, J=8 Hz), 7.11 (H, m), 7.21 (1H, d, J=8.5 Hz), 7.39 (1H, m), 7.62-7.63 (2H, m), 7.76 (1H, d, J=7.9 Hz), 8.82 (1H, s).

Workup

  1. waitat room temperature for 10 min
  2. temperatureThe mixture was then cooled back to 0° C.
  3. stirringThe mixture was stirred at 0° C. for 5 min
  4. waitat room temperature for 10 min
  5. filtrationThe mixture was filtered
  6. customthe filtrate evaporated in vacuo
  7. customThe residue was partitioned between ethyl acetate (30 ml) and water (30 ml)
  8. filtrationan undissolved solid filtered off
  9. customThe organic phase from the filtrate was separated
  10. washthe aqueous phase washed once more with ethyl acetate (10 ml)
  11. washThe combined organic layers were washed with brine (20 ml)
  12. dry with materialdried (Na2SO4)
  13. customevaporated in vacuo
  14. customThe residue was chromatographed on silica gel using 95:5:1 dichloromethane

Sources & evidence

ORD record
ord-f1762313709d41049dd7655b53179b84
Source dataset
uspto-grants-1996_09
Patent number
US05556969

Reaction notes

Loading…