4-Methylmorpholine → HCID 67773711, compound
Reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[F:41][C:42]1([F:53])[CH2:46][CH2:45][N:44]([CH2:47][C@@H:48]([NH2:52])[CH:49]([CH3:51])[CH3:50])[CH2:43]1>CN(C=O)C>[F:53][C:42]1([F:41])[CH2:46][CH2:45][N:44]([CH2:47][C@@H:48]([NH:52][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([CH3:1])[CH:3]=2)[CH:49]([CH3:50])[CH3:51])[CH2:43]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
3,4-Dimethylbenzoic acid (130 mg, 0.87 mmol) and TBTU (279 mg, 0.87 mmol) was mixed in DMF (1.5 mL). The mixture was cooled to 0° C. and NMM (0.287 mL, 2.61 mmol) was dropwise added. After 10 min at 0° C. was (S)-1-(3,3-difluoropyrrolidin-1-yl)-3-methylbutan-2-amine (Compound O) (167 mg, 0.87 mmol) added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM (5 mL). The organic phase was washed with HCl (1M aq. solution, 5 mL), NaHCO3 (saturated, 2×5 mL) and brine (5 mL), and filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (143 mg, 51%). 1H NMR (400 MHz, DMSO-d6) δ 0.65-1.03, 1.61-1.92, 2.00-2.21, 2.23, 2.53-3.03, 3.66-4.22, 7.19, 7.55, 7.61, 7.87. Total no of protons: 26.
Workup
- concentrationThe mixture was concentrated
- dissolutionthe residue dissolved in DCM (5 mL)
- washThe organic phase was washed with HCl (1M aq. solution, 5 mL), NaHCO3 (saturated, 2×5 mL) and brine (5 mL)
- filtrationfiltered through a phase separator
- concentrationconcentrated under reduced pressure
- customThe residue was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-99f4501a355843fabfd26ca7e4cdef19
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08361998B2
Reaction notes
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