Sodium Iodide → 2-chloro-5-[2-[(3-hydroxypropyl)amino]ethoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

HRID 2085641Notes

Reaction equation

HRID 2085641 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24]Cl)=[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].C(N(CC)C(C)C)(C)C.[I-].[Na+].[NH2:37][CH2:38][CH2:39][CH2:40][OH:41]>C(O)CCC>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][NH:37][CH2:38][CH2:39][CH2:40][OH:41])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:15][CH:14]3[CH2:13][CH:12]([CH2:11][CH:10]([CH2:16]3)[CH2:9]1)[CH2:17]2)=[O:5]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 90863-Amino-1-propanolHCID 81531DiisopropylethylamineHCID 227314842-chloro-5-(2-chloroethoxy)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 102263002-chloro-5-[2-[(3-hydroxypropyl)amino]ethoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-chloro-5-[2-chloroethoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (Example 11a, 0.15 g) and N,N-diisopropylethylamine (0.50 ml) in 1-butanol (4 ml) was added sodium iodide (0.06 g) and 3-aminopropan-1-ol (0.09 ml). The reaction vessel was sealed and the mixture heated at 110° C. for 24 h. The reaction mixture was partitioned between ethyl acetate and sodium hydrogencarbonate solution, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by RPHPLC (eluting with 25-95% MeCN/0.1% AcONH4 aqueous) to give 2-chloro-5-[2-[(3-hydroxypropyl)amino]ethoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide as the acetate salt. This was converted to the hydrochloride salt by stirring with 4M HCl in dioxane and concentration under reduced pressure. Recrystalisation from isohexane/isopropanol gave the title compound as a white solid (0.1 g).

Workup

  1. customThe reaction vessel was sealed
  2. customThe reaction mixture was partitioned between ethyl acetate and sodium hydrogencarbonate solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by RPHPLC (eluting with 25-95% MeCN/0.1% AcONH4 aqueous)

Sources & evidence

ORD record
ord-7ec07bb5dd5e46dfb1211edf7657e203
Source dataset
uspto-grants-2004_04
Patent number
US06720452B2

Reaction notes

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