Ethanol → 3-(4-Propoxy-1H-pyrazol-3-yl)-1-azabicyclo[2.2.2]octane
Reaction equation
[CH2:1]([O:5][C:6]1[C:7]([CH:11]2[CH:16]3[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]3)[CH2:12]2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH2:3]C.C(O)CC.IC1C(C2C3CCN(CC3)C2)=NN(COCC[Si](C)(C)C)C=1.CCO>CCO.C(OCC)(=O)C.C(N(CC)CC)C.CCO.C(N(CC)CC)C>[CH2:1]([O:5][C:6]1[C:7]([CH:11]2[CH:16]3[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]3)[CH2:12]2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH3:3]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
Compound 52B was prepared following the procedure as described for the synthesis of compound 52A (see Scheme 10) using propanol and 3-[4-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-3-yl]-1-azabicyclo[2.2.2]octane (50). Work-up and flash chromatography (gradient EtOH to EtOH/triethylamine 300/1) followed by a second flash chromatography (EtOH/ethyl acetate/triethylamine 25/75/1) afforded compound 51B as an oil (14%). LCMS (method B): Rt: 7.15 min, ([M+H]+=366). Compound 51A was subsequently deprotected (TBAF/THF) and purified by flash chromatography (gradient EtOH to EtOH/triethylamine 97/3), followed by a preperative TLC purification (CH3CN/H2O) to afford the title compound 52B as an oil. (51%). LCMS (method A); Rt: 0.91 min, ([M+H]+=236). 1H-NMR (600 MHz, D6DMSO): δ 7.34 (s, 1H), 3.74 (t, J=7 Hz, 2H), 3.24-3.19 (m, 1H), 3.03-2.96 (m, 1H), 2.92-2.87 (m, 1H), 2.86-2.74 (m, 3H), 2.69-2.62 (m, 1H), 1.88-1.84 (m, 1H), 1.67-1.55 (m, 5H), 1.26-1.20 (m, 1H), 0.92 (t, J=7 Hz, 3H).
Sources & evidence
- ORD record
- ord-6882c425137a4d94b3da2931d667ad3e
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735388B2
Reaction notes
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