p-Toluenesulfonic acid → 2-Chloro-5-[[[3-[(1-methylethyl)amino]propyl]amino]methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

HRID 1816059Notes

Reaction equation

HRID 1816059 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH:22]=O)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[CH:24]([NH:27][CH2:28][CH2:29][CH2:30][NH2:31])([CH3:26])[CH3:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][NH:31][CH2:30][CH2:29][CH2:28][NH:27][CH:24]([CH3:26])[CH3:25])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:11][CH:10]([CH2:16][CH:14]([CH2:13]3)[CH2:15]1)[CH2:9]2)=[O:5]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 76888N-Isopropylpropane-1,3-diamineHCID 120853462-Chloro-5-formyl-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 101136262-Chloro-5-[[[3-[(1-methylethyl)amino]propyl]amino]methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamideYield 4.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-chloro-5-formyl-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.244 g, Example 25b), N-isopropyl-1,3-propanediamine (0.211 g), p-toluenesulfonic acid (0.005 g) and toluene (30 ml) were refluxed together under Dean-Stark conditions for 3 h. The mixture was cooled and concentrated under reduced pressure to an oil. This was dissolved in ethanol (30 ml) and cooled to 0° C. under a nitrogen atmosphere. Solid sodium borohydride (0.040 g) was added portionwise and the mixture stirred at room temperature for 30 min, then concentrated under reduced pressure and the residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia) to give the title compound (0.015 g) and a by-product (see Example 27).

Workup

  1. temperaturewere refluxed together under Dean-Stark conditions for 3 h
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated under reduced pressure to an oil
  4. dissolutionThis was dissolved in ethanol (30 ml)
  5. additionSolid sodium borohydride (0.040 g) was added portionwise
  6. concentrationconcentrated under reduced pressure
  7. customthe residue purified by column chromatography over silica (eluting with 9:1:0.1 dichloromethane/methanol/35% aqueous ammonia)

Sources & evidence

ORD record
ord-01694d23576447bf88f7306ce7c42062
Source dataset
uspto-grants-2005_04
Patent number
US06881754B2

Reaction notes

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