Methylamine → 2-Chloro-5-[3-(methylamino)propyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide, acetate salt
Reaction equation
[CH3:1][NH2:2].[Cl:3][C:4]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26]OS(C)(=O)=O)=[CH:20][C:5]=1[C:6]([NH:8][CH2:9][C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][CH:12]([CH2:13]3)[CH2:11]1)[CH2:17]2)=[O:7].[C:32]([O:35]CC)(=[O:34])[CH3:33]>>[C:32]([OH:35])(=[O:34])[CH3:33].[Cl:3][C:4]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][NH:2][CH3:1])=[CH:20][C:5]=1[C:6]([NH:8][CH2:9][C:10]12[CH2:19][CH:14]3[CH2:13][CH:12]([CH2:18][CH:16]([CH2:15]3)[CH2:17]1)[CH2:11]2)=[O:7]Participants
4
Conditions
- Temperature
- 70 °C
Procedure
Methylamine (2M tetrahydrofuran, 8 ml) was added to 2-chloro-5-[3-[(methylsulfonyl)oxy]propyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.250 g, Example 6e) and heated in a sealed tube at 70° C. for 18 h. On cooling to ambient temperature, the solution was diluted with ethyl acetate and extracted twice with saturated sodium hydrogencarbonate solution and once with brine, dried over magnesium sulfate and concentrated under reduced pressure. Purification by preparative reverse phase HPLC (eluting with a gradient of acetonitrile in 0.1% aqueous ammonium acetate/25–95%) gave the title compound as the acetate salt (0.140 g).
Workup
- temperatureOn cooling to ambient temperature
- extractionextracted twice with saturated sodium hydrogencarbonate solution and once with brine
- dry with materialdried over magnesium sulfate
- concentrationconcentrated under reduced pressure
- customPurification by preparative reverse phase HPLC (
- washeluting with a gradient of acetonitrile in 0.1% aqueous ammonium acetate/25–95%)
Sources & evidence
- ORD record
- ord-eb6129af4ddc4a4fb30abb3afe68b78c
- Source dataset
- uspto-grants-2006_11
- Patent number
- US07132457B2
Reaction notes
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