Hydrochloric Acid → 1-[5-Chloro-3-(1-isopropylazetidin-3-yl)-2-methoxy-4-methylphenyl]ethanamine dihydrochloride
Reaction equation
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([CH:20]2[CH2:23][N:22]([CH:24]([CH3:26])[CH3:25])[CH2:21]2)[C:5]([O:18][CH3:19])=[C:6]([CH:8]([NH:10]C(=O)OC(C)(C)C)[CH3:9])[CH:7]=1.[ClH:28].O1CCOCC1>C(Cl)Cl>[ClH:1].[ClH:28].[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([CH:20]2[CH2:21][N:22]([CH:24]([CH3:26])[CH3:25])[CH2:23]2)[C:5]([O:18][CH3:19])=[C:6]([CH:8]([NH2:10])[CH3:9])[CH:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
tert-Butyl {1-[5-chloro-3-(1-isopropylazetidin-3-yl)-2-methoxy-4-methylphenyl]ethyl}carbamate (19 mg, 0.048 mmol) was treated with 4.0 M HCl in dioxane (60 μL, 0.24 mmol) in methylene chloride (50 μL) at room temperature for 2 hours. The resultant mixture was concentrated to dryness to give 1-[5-chloro-3-(1-isopropylazetidin-3-yl)-2-methoxy-4-methylphenyl]ethanamine dihydrochloride. A mixture of the HCl salt, 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (20 mg, 0.072 mmol, from Example 108, Step 1) and DIPEA (42 μL, 0.24 mmol) in ethanol (0.3 mL) was heated at 100° C. overnight. The mixture was treated with 6.0 M HCl in water (80 μL, 0.5 mmol) at room temperature for 10 min and then purified on prep-LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.05% trifluoroacetic acid, at flow rate of 30 mL/min) to afford the desired product as TFA salt. LCMS calculated for C21H28ClN6O (M+H)+: m/z=415.2. found: 415.1.
Workup
- concentrationThe resultant mixture was concentrated to dryness
Sources & evidence
- ORD record
- ord-42ae7c5961014687a5043034c98cd5b8
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096600B2
Reaction notes
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