3-Amino-1-propanol → AZD-9056 hydrochloride

HRID 1816044Notes

Reaction equation

HRID 1816044 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[Cl:6][C:7]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29]OS(C)(=O)=O)=[CH:23][C:8]=1[C:9]([NH:11][CH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:10]>O1CCCC1.O>[ClH:6].[Cl:6][C:7]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29][NH:1][CH2:2][CH2:3][CH2:4][OH:5])=[CH:23][C:8]=1[C:9]([NH:11][CH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:10]

Participants

5

Reactant 2

HCID 90863-Amino-1-propanolHCID 12988688chloro-5-[3-[(methylsulfonyl)oxy]propyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 10161380AZD-9056 hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Aminopropanol (1 ml) was added to a solution of 2-chloro-5-[3-[(methylsulfonyl)oxy]propyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.270 g, Example 6e) in tetrahydrofuran (30 ml) and the solution heated at reflux for 12 h. On cooling to ambient temperature the reaction mixture was diluted with water and extracted thrice with dichloromethane. The organic extracts were combined, dried over magnesium sulfate and concentrated under reduced pressure. Purification by preparative reverse phase HPLC eluting with a gradient of acetonitrile/0.1% aqueous ammonium acetate (25-95%), gave the title compound as the acetate salt. Treatment with 4M hydrochloric acid in dioxane gave the title compound as the hydrochloride salt (0.070 g).

Workup

  1. temperaturethe solution heated
  2. temperatureat reflux for 12 h
  3. extractionextracted thrice with dichloromethane
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by preparative reverse phase HPLC
  7. washeluting with a gradient of acetonitrile/0.1% aqueous ammonium acetate (25-95%)

Sources & evidence

ORD record
ord-e092bdad2edb457f8f445111e61b823c
Source dataset
uspto-grants-2005_04
Patent number
US06881754B2

Reaction notes

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