Hydrochloric Acid → N-(2-Aminoethyl){-6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthalenecarboxamide}

HRID 990794Notes

Reaction equation

HRID 990794 reaction equation
[C:1]12([C:11]3[CH:12]=[C:13]([C:19]4[CH:20]=[C:21]5[C:26](=[CH:27][CH:28]=4)[CH:25]=[C:24]([C:29](O)=[O:30])[CH:23]=[CH:22]5)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.S(Cl)(Cl)=O.[CH2:36]([NH2:39])[CH2:37][NH2:38].Cl>C1(C)C=CC=CC=1.C(Cl)Cl.CN(C=O)C>[NH2:38][CH2:37][CH2:36][NH:39][C:29]([C:24]1[CH:23]=[CH:22][C:21]2[C:26](=[CH:27][CH:28]=[C:19]([C:13]3[CH:14]=[CH:15][C:16]([O:17][CH3:18])=[C:11]([C:1]45[CH2:10][CH:5]6[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]6)[CH2:8]4)[CH2:2]5)[CH:12]=3)[CH:20]=2)[CH:25]=1)=[O:30]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3301EthylenediamineHCID 24386Thionyl Chloride2×HCID 60164Adapalene

Product 1

HCID 10226132N-(2-Aminoethyl){-6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthalenecarboxamide}

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthalenecarboxylic acid (3 g, 7.27 mmoles) in dry toluene (20 mL) was added thionyl chloride (0.6 mL, 8.22 mmoles) and DMF (0.04 mL) under argon. The reaction mixture was heated to 100° C. for ten minutes and another 0.04 mL of DMF was added. After 30 minutes, more thionyl chloride (0.1 mL, 1.37 mmoles) was added and the reaction mixture was heated to 110° C. for 60 minutes. The solvent and excess thionyl chloride were removed in vacuo. The resulting solid was stirred with 100 mL dry methylene chloride under argon. This was added to a mixture of ethylene diamine (5.25 mL, 70 mmoles) in dry methylene chloride under argon at 0° C. while stirring rapidly. The solution was allowed to warm to ambient temperature while stirring rapidly during one hour. The reaction mixture was poured carefully into 350 mL of 1N aqueous HCl while stirring, and the methylene chloride was removed in vacuo. The resulting precipitate (hydrochloride salt of the product) was washed with 1N HCl, water, THF, and methylene chloride. Yield of hydrochloride salt: 2.76 g, 77%. The free base was generated by neutralizing with aqueous sodium bicarbonate and extracting the product into tetrahydrofuran, drying the organic layer over sodium sulfate, and removing the solvent. MS 455 (M+H+).

Workup

  1. temperaturethe reaction mixture was heated to 110° C. for 60 minutes
  2. customThe solvent and excess thionyl chloride were removed in vacuo
  3. stirringwhile stirring rapidly
  4. temperatureto warm to ambient temperature
  5. stirringwhile stirring rapidly during one hour
  6. stirringwhile stirring
  7. customthe methylene chloride was removed in vacuo
  8. washThe resulting precipitate (hydrochloride salt of the product) was washed with 1N HCl, water, THF, and methylene chloride
  9. extractionextracting the product into tetrahydrofuran
  10. dry with materialdrying the organic layer over sodium sulfate
  11. customremoving the solvent

Sources & evidence

ORD record
ord-69e690966a11431a93ab3ed679173efa
Source dataset
uspto-grants-2002_10
Patent number
US06462064B1

Reaction notes

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