Ethanol → 2-chloro-5-[3-(3-hydroxy-propylamino)-propoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

HRID 2085636Notes

Reaction equation

HRID 2085636 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25]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:30]([CH2:34][CH3:35])C(C)C)(C)C.[I-].[Na+].[CH2:38]([OH:40])C>>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][NH:30][CH2:34][CH2:35][CH2:38][OH:40])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:9][CH:10]3[CH2:16][CH:14]([CH2:13][CH:12]([CH2:11]3)[CH2:17]1)[CH2:15]2)=[O:5]

Participants

5

Reactant 4

HCID 702EthanolHCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 227314912-chloro-5-[3-chloropropoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 102769622-chloro-5-[3-(3-hydroxy-propylamino)-propoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Conditions

Temperature
120 °C

Procedure

To a solution of 2-chloro-5-[3-chloropropoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.25 g, Example 3a) and N,N-diisopropylethylamine (0.54 ml) in ethanol (5 ml) was added sodium iodide (0.08 g) and 1-propanolamine (0.24 ml). The reaction vessel was sealed and reaction mixture heated at 120° C. for 24 h. The reaction mixture was then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution, and the aqueous phase extracted with additional ethyl acetate. The combined organic phases were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane) to give 2-chloro-5-[3-(3-hydroxy-propylamino)-propoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide as a semi-solid. This compound was converted to the hydrochloride salt by stirring with 4M HCl in dioxane and concentrated under reduced pressure to leave the title compound as a white solid (0.036 g).

Workup

  1. customThe reaction vessel was sealed
  2. customreaction mixture
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution
  5. extractionthe aqueous phase extracted with additional ethyl acetate
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane)

Sources & evidence

ORD record
ord-31e9a60501f646f8863522b100d4c0cc
Source dataset
uspto-grants-2004_04
Patent number
US06720452B2

Reaction notes

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