1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol

HRID 55396

Reaction equation

HRID 55396 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([OH:19])[CH2:17][CH:16]([CH3:18])[CH2:15][CH:14]2[CH:10]1[CH2:11][NH:12][CH2:13]2.[CH3:20][N:21]([CH3:32])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][C:29](O)=[O:30].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([OH:19])[CH2:17][CH:16]([CH3:18])[CH2:15][CH:14]2[CH:10]1[CH2:11][N:12]([C:29](=[O:30])[CH2:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[N:21]([CH3:32])[CH3:20])[CH2:13]2

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 19957564(3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-6-methyl-4 perhydroisoindololHCID 204661092-(2-(Dimethylamino)phenyl)acetic acid

Product 1

HCID 19957561(3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindololYield 71.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 0.78 g of (3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol in 80 cm3 of dichloromethane is added 0.5 cm3 of triethylamine. The reaction mixture is cooled to 5° C. and 0.54 g of (2-dimethylaminophenyl)acetic acid, 0.05 g of 1-hydroxybenzotriazole monohydrate and 0.63 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added. The reaction mixture is maintained for 1 hour at 5° C. and for 16 hours at 20° C. and is then washed twice with 100 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm), eluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol [97.5/2.5 by volume] and collecting 65 cm3 fractions. Fractions 17 to 23 are concentrated and, after drying at 40° C. at 15 Pa, 0.90 g of (3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol is obtained in the form of a white powder which is dissolved in 50 cm3 of dioxane. 3 cm3 of 5M hydrochloric acid solution in dioxane are added and, after 1 hour at room temperature, the solution is concentrated under reduced pressure (2.7 kPa), triturated in isopropyl ether, filtered and dried at 40° C. at 15 Pa. 1.0 g of (3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-2-[(2-dimethylaminophenyl)acetyl]-6-methyl-4-perhydroisoindolol hydrochloride is obtained.

Workup

  1. temperatureThe reaction mixture is maintained for 1 hour at 5° C. and for 16 hours at 20° C.
  2. washis then washed twice with 100 cm3 of water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 50 cm)
  7. washeluting under a pressure of 0.7 bar with a mixture of dichloromethane and methanol [97.5/2.5 by volume]
  8. customcollecting 65 cm3 fractions
  9. concentrationFractions 17 to 23 are concentrated
  10. customafter drying at 40° C. at 15 Pa

Sources & evidence

ORD record
ord-8217e49da5c843919352709a35ea980b
Source dataset
uspto-grants-1997_04
Patent number
US05624950

Linked notes

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