Morpholine → N-[5-(3-Methoxy-phenyl)-1H-pyrazol-3-yl]-4-morpholin-4-yl-butyramide
Reaction equation
COC1C=C(C2C=C(N)NN=2)C=CC=1.C(N(C(C)C)CC)(C)C.Br[CH2:25][CH2:26][CH2:27][C:28]([NH:30][C:31]1[CH:35]=[C:34]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([O:42][CH3:43])[CH:37]=2)[NH:33][N:32]=1)=[O:29].[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>CC(N(C)C)=O.C(Cl)Cl>[CH3:43][O:42][C:38]1[CH:37]=[C:36]([C:34]2[NH:33][N:32]=[C:31]([NH:30][C:28](=[O:29])[CH2:27][CH2:26][CH2:25][N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)[CH:35]=2)[CH:41]=[CH:40][CH:39]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 60 °C
Procedure
A solution of 4-bromobutyryl chloride chloride (0.104 mL, 0.9 mmol) in dry DMA (1 mL) was cooled to −10° C. (ice/water bath) under N2; 5-(3-methoxy-phenyl)-2H-pyrazol-3-ylamine (170 mg, 0.9 mmol) and diisopropylethylamine (0.315 mL, 1.8 mmol) in dry DMA (1 ml) were added. Upon complete conversion to the intermediate 4-bromo-N-[5-(3-methoxy-phenyl)-1H-pyrazol-3-yl]-butyramide (as monitored by LC-MS), morpholine (0.079 mL, 0.9 mmol) was added and the mixture was heated at 60° C. for 16 hours. The residue was dissolved in DCM (2 mL) and washed with sat. Na2CO3 solution, The organic phase was concentrated under reduced pressure and the crude product was purified by SiO2 column (gradient from Acetonitrile 100% to MeCN/MeOH, NH3 90/10). The fractions containing the title compound were collected to afford 17 mg (5.5% of yield).
Workup
- washwashed with sat. Na2CO3 solution
- concentrationThe organic phase was concentrated under reduced pressure
- customthe crude product was purified by SiO2 column (gradient from Acetonitrile 100% to MeCN/MeOH, NH3 90/10)
- additionThe fractions containing the title compound
- customwere collected
- customto afford
- custom17 mg (5.5% of yield)
Sources & evidence
- ORD record
- ord-51f93f3ebe0040c5bece6048fd271d5b
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08163729B2
Reaction notes
Loading…