Piperazine → HCID 79016966, compound
Reaction equation
Cl[C:2]1[CH:12]=[CH:11][C:5]([C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[CH:4][N:3]=1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:9][N:8]([CH3:10])[C:6]([C:5]1[CH:4]=[N:3][C:2]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:12][CH:11]=1)=[O:7]Participants
Conditions
- Temperature
- 70 °C
Procedure
A solution of 6-chloro-N,N-dimethylnicotinamide (250 mg, 1.354 mmol), piperazine (584 mg, 6.77 mmol), sodium tert-butoxide (260 mg, 2.71 mmol) and BrettPhos (36 mg, 0.068 mmol) in anhydrous 1,4-dioxane (7 ml) was purged with argon. Next, Pd2(DBA)3 (62 mg, 0.068 mmol) was added and the mixture was heated in a closed vial to 70° C. for 2 hours, then heating was turned off and the mixture was stirred at room temperature for 3 days. The mixture was filtered through kieselguhr, the filter was washed with ethyl acetate, the combined filtrates were concentrated under reduced pressure and the residue was purified by repeated column chromatography (silica, gradient from 1 to 10% methanol containing 7N ammonia in DCM) to yield 158 mg of a solid (0.674 mmol, 50% yield) MS (multi-mode) m/z=235.2 [M+1]+.
Workup
- temperatureheating
- filtrationThe mixture was filtered through kieselguhr
- washthe filter was washed with ethyl acetate
- concentrationthe combined filtrates were concentrated under reduced pressure
- customthe residue was purified
Sources & evidence
- ORD record
- ord-22cf0b2334a845aca08f4bdaa837ebb6
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09260441B2
Reaction notes
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