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

HRID 1593813Notes

Reaction equation

HRID 1593813 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 (1ml) 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 to 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 preperative 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 4 M hydrochloric acid in dioxane gave the title compound as the hydrochloride salt (0.070 g).

Workup

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

Sources & evidence

ORD record
ord-11be46d58fe54e2c83b3b943791c313b
Source dataset
uspto-grants-2007_11
Patent number
US07297818B2

Reaction notes

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