Diisopropylethylamine → HCID 59863025, compound
Reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6](F)[CH:5]=2)[CH2:3][CH2:2]1.Cl.Cl.[O:16]1[CH2:21][CH2:20][CH:19]([N:22]2[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]2)[CH2:18][CH2:17]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6]([NH:28][CH:25]3[CH2:24][CH2:23][N:22]([CH:19]4[CH2:20][CH2:21][O:16][CH2:17][CH2:18]4)[CH2:27][CH2:26]3)[CH:5]=2)[CH2:3][CH2:2]1Participants
Conditions
- Temperature
- 90 °C
Procedure
A stirred mixture of 4-cyclopropyl-2-fluoro-1-nitrobenzene (D37, 180 mg, 0.99 mmol), 1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine dihydrochloride (diHCl salt of D9, 280 mg, 1.1 mmol) and N,N-diisopropylethylamine (0.56 ml, 3.3 mmol), in dimethylformamide (5 ml) was stirred at room temperature for 3 hrs, then heated at 90° C. for 18 hrs. The cooled mixture was concentrated under vacuum and the residue treated with dilute K2CO3 solution (20 ml) and extracted with ethyl acetate (3×30 ml). The combined extract was washed with water, dried (MgSO4) and concentrated under vacuum. The residue was purified by chromatography on silica gel (40 g) eluting with 1-10% methanol/dichloromethane to afford the title compound as an orange solid (200 mg, 59%). M++H=346.0.
Workup
- concentrationThe cooled mixture was concentrated under vacuum
- additionthe residue treated with dilute K2CO3 solution (20 ml)
- extractionextracted with ethyl acetate (3×30 ml)
- extractionThe combined extract
- washwas washed with water
- dry with materialdried (MgSO4)
- concentrationconcentrated under vacuum
- customThe residue was purified by chromatography on silica gel (40 g)
- washeluting with 1-10% methanol/dichloromethane
Sources & evidence
- ORD record
- ord-0b8d0518525f4f58b1693c66e6733de8
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288413B2
Reaction notes
Loading…