Dichloromethane → HCID 68278176, compound

HRID 530463Notes

Reaction equation

HRID 530463 reaction equation
[CH3:1][CH2:2][N:3]=[C:4]=[N:5][CH2:6][CH2:7][CH2:8][N:9]([CH3:11])[CH3:10].Cl.[CH2:13]1[CH:17]2C3C(=O)N(O)C(=O)C3[CH:14]1C=C2.[CH3:26][NH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[NH2:34].[CH3:35][CH2:36][N:37]([CH:41]([CH3:43])C)[CH:38]([CH3:40])[CH3:39].[CH2:44](Cl)Cl>>[CH3:26][N:27]1[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[N:34]=[C:1]1[C:2]1[CH:17]=[CH:13][CH:14]=[C:4]([N:5]2[CH2:6][CH2:7][CH2:8][N:9]([CH:11]3[CH2:35][CH2:36][N:37]([CH:38]([CH3:39])[CH3:40])[CH2:41][CH2:43]3)[CH2:10][CH2:44]2)[N:3]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 78498N-Methyl-o-phenylenediamineHCID 81531DiisopropylethylamineHCID 895293a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dioneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 68278176HCID 68278176, compoundYield 18%

Conditions

Temperature
45 °C

Procedure

Intermediate 135 (200 mg, 0.58 mmol), EDC.HCl (167 mg, 0.87 mmol), HONB (156 mg, 0.87 mmol), N-methyl-1,2-phenylenediamine (177 mg, 1.45 mmol) and DIPEA (144 mL, 0.87 mmol) were dissolved in DCM (4 mL) and stirred at 45° C. in a sealed tube overnight. The reaction mixture was diluted with DCM (20 mL), washed with sat aq NaHCO3 (25 mL), brine (25 mL) and concentrated in vacuo. The residue was purified by column chromatography, dissolved in acetic acid (2 mL) and heated using a microwave (150° C., absorption high) for 30 min. The solvents were removed in vacuo and the residue dissolved in DCM (25 mL), washed with sat aq NaHCO3 (25 mL), brine (25 mL) and concentrated in vacuo. The product was purified by reverse phase HPLC to give the title compound (44.3 mg, 18%) as a colourless gum. HRMS (ESI+) calculated for C26H36N6; 433.30742. found 433.30667. HPLC: Rf 3.66 min, 100% purity.

Workup

  1. washwashed
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography
  4. dissolutiondissolved in acetic acid (2 mL)
  5. temperatureheated
  6. customa microwave (150° C., absorption high) for 30 min
  7. customThe solvents were removed in vacuo
  8. dissolutionthe residue dissolved in DCM (25 mL)
  9. washwashed
  10. concentrationconcentrated in vacuo
  11. customThe product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1944d72ea67d4f63a21e44cf72a94a8a
Source dataset
uspto-grants-2016_05
Patent number
US09353086B2

Reaction notes

Loading…