4-Methylmorpholine → 6-Phenyl-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamide

HRID 602073Notes

Reaction equation

HRID 602073 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[F:38][C:39]([F:49])([F:48])[CH2:40][N:41]1[CH2:46][CH2:45][CH:44]([NH2:47])[CH2:43][CH2:42]1.CN1CCOCC1>CN(C)C(=O)C.O>[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:47][CH:44]3[CH2:45][CH2:46][N:41]([CH2:40][C:39]([F:49])([F:38])[F:48])[CH2:42][CH2:43]3)=[O:15])=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1201186-Phenylnicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162287221-(2,2,2-Trifluoroethyl)piperidin-4-amine

Product 1

HCID 597438866-Phenyl-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamideYield 84.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a 250 mL 3-necked flask containing 2-phenyl-5-pyridinecarboxylic acid (2.75 g, 13.8 mmol) in N,N-dimethylacetamide (DMA, 35 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC/EDC*HCl, 2.95 g, 15.2 mmol), 1-hydroxybenzotriazole (HOBt. 1.89 g, 13.8 mmol), 1-(2,2,2-trifluoroethyl)piperidin-4-amine (3.36 g, 15.2 mmol) and 4-methylmorpholine (NMM, 3.8 mL, 34.5 mmol). After stirring at room temperature for 1 hour, the reaction was diluted with water (˜200 mL) and the resulting solid collected by filtration. The solid was washed with H2O (3×100 mL), collected and dried in a vacuum oven (45° C.) overnight to give the desired product (4.24 g). LCMS (ES+) 4.30 min (TIC, 75%; 1H NMR purity >95%); 1H NMR (400 MHz, DMSO-d6) □ ppm 1.46-1.65 (m, 2H) 1.77 (d, J=10.80 Hz, 2 H) 2.31-2.54 (m, 4H) 2.90 (d, J=11.53 Hz, 2H) 3.65-3.86 (m, 1H) 7.36-7.56 (m, 3H) 8.01 (d, J=8.24 Hz, 1H) 8.09 (d, J=6.95 Hz, 2H) 8.22 (d, J=8.42 Hz, 1H) 8.38 (d, J=7.32 Hz, 1H) 9.02 (s, 1 H); MS(ES+) 364 (M+1); HRMS (TOF, ES+) calculated for C19H20F3N3O+H+: 364.1637; observed 364.1611.

Workup

  1. filtrationthe resulting solid collected by filtration
  2. washThe solid was washed with H2O (3×100 mL)
  3. customcollected
  4. customdried in a vacuum oven (45° C.) overnight

Sources & evidence

ORD record
ord-b82023ae1fe640e6998883d65100afb4
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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