Diisopropylethylamine → HCID 68972293, compound
Reaction equation
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][N:14]([C@H:17]([CH3:21])[CH2:18][C:19]#[N:20])[CH2:13][CH2:12]2)=[CH:6][CH:5]=1.Cl.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=1.CCN(C(C)C)C(C)C>C1COCC1>[C:19]([CH2:18][C@H:17]([N:14]1[CH2:15][CH2:16][CH:11]([N:10]([C:7]2[CH:6]=[CH:5][C:4]([O:3][CH:2]([F:1])[F:22])=[CH:9][CH:8]=2)[C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=2)[CH2:12][CH2:13]1)[CH3:21])#[N:20]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A solution of the above nitrile (0.20 g, 0.65 mmol) and nicotinoyl chloride hydrochloride (0.46 g, 2.6 mmol) in THF (6 mL) was then treated with DIPEA (0.56 mL, 3.2 mmol) and stirred at 80° C. for 16 h. The reaction was cooled to room temperature, concentrated under reduced pressure, diluted with CH2Cl2 (10 mL) and washed with brine solution (2×10 mL). The combined organic extracts were then dried (Na2SO4), filtered and concentrated and the crude material purified by flash column chromatography on silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH) to afford N-[(R)-1-(2-cyano-1-methyl-ethyl)-piperidin-4-yl]-N-(4-difluoromethoxy-phenyl)-nicotinamide as a pale yellow oil (104 mg, 39%).
Workup
- temperatureThe reaction was cooled to room temperature
- concentrationconcentrated under reduced pressure
- additiondiluted with CH2Cl2 (10 mL)
- washwashed with brine solution (2×10 mL)
- dry with materialThe combined organic extracts were then dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customthe crude material purified by flash column chromatography on silica gel (50:1:0.1 CH2Cl2/MeOH/NH4OH)
Sources & evidence
- ORD record
- ord-509ba96307904656baf9865e99f729ea
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07498346B2
Reaction notes
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