Lithium → (4-Isopropyl-yl)-(1-methyl-4-piperidin-1-ylmethyl-1Hpyrrol-2-yl)-methanone
Reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[N:16]([CH3:17])[CH:15]=[C:14]([CH:18]=O)[CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C([C:22]1[CH:23]=[C:24]([C:28](O)=O)[N:25](C)[CH:26]=1)=O.[Li].Cl.Cl.C(N1CCNCC1)(C)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[N:16]([CH3:17])[CH:15]=[C:14]([CH2:18][N:25]3[CH2:26][CH2:22][CH2:23][CH2:28][CH2:24]3)[CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
5-(4-Isopropyl-piperazine-1-carbonyl)-1-methyl-1H-pyrrole-3-carbaldehyde. 4-Formyl-1-methyl-1H-pyrrole-2-carboxylic acid, lithium salt, (1.08 g.) was diluted with thionyl chloride (20 mL) and heated at reflux under nitrogen for 1.5 h. The reaction mixture was carefully concentrated. The residue was co-evaporated with toluene (3×) to remove residual HCl, and then was kept under vacuum for 2 h. Separately, a solution of 1-isopropyl-piperazine dihydrochloride (1.21 g, 6.00 mmol) in DCM (50 mL) was cooled to 0-5° C. TEA (2.23 mL, 24.0 mmol) was added slowly, followed by the above acid chloride solution in DCM (50 mL). The resulting mixture was allowed to stir overnight at rt. The mixture was concentrated to yield the crude product (3.78 g), which was purified on silica gel column using 2-6% 2 M NH3 in MeOH/DCM to yield the title compound (0.20 g).
Workup
- temperatureheated
- temperatureat reflux under nitrogen for 1.5 h
- concentrationThe reaction mixture was carefully concentrated
- customto remove residual HCl
- concentrationThe mixture was concentrated
- customto yield the crude product (3.78 g), which
- customwas purified on silica gel column
Sources & evidence
- ORD record
- ord-d87d55457cea428a83e4b5e3102c0170
- Source dataset
- uspto-grants-2008_09
- Patent number
- US07429659B2
Reaction notes
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