4-Methylmorpholine → 6-(2,5-difluorophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamide

HRID 602096Notes

Reaction equation

HRID 602096 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=1.[F:18][C:19]([F:29])([F:28])[CH2:20][N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CCOC(C)=O.O.CC(N(C)C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:27][CH:24]2[CH2:25][CH2:26][N:21]([CH2:20][C:19]([F:29])([F:18])[F:28])[CH2:22][CH2:23]2)=[O:15])=[CH:11][N:10]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 162287221-(2,2,2-Trifluoroethyl)piperidin-4-amineHCID 247299846-(2,5-Difluorophenyl)nicotinic acid

Product 1

HCID 597438216-(2,5-difluorophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a 50 mL flask was added 6-(2,5-difluorophenyl)nicotinic acid (100 mg, 0.46 mmol), 1-(2,2,2-trifluoroethyl)piperidin-4-amine (77.5 mg, 0.46 mmol), EDAC (89.7 mg, 0.468 mmol), HOBT (57.5 mg, 0.46 mmol), and DMA (2 mL) followed by NMM (0.117 mL, 1.06 mmol). The reaction was stirred for 1 hour at room temperature and then diluted with EtOAc (0.2 mL) followed by H2O (4 mL). The resulting solids were washed in H2O and collected by filtration. 1H NMR (400 MHz, DMSO-d6) □ ppm 9.12 (1H, d, J=2.2 Hz), 8.55 (1H, d, J=7.5 Hz), 8.31 (1H, dd, J=8.3, 2.3 Hz), 7.95 (1 H, dd, J=8.2, 1.5 Hz), 7.73-7.84 (1H, m), 7.35-7.51 (2H, m), 3.73-3.90 (1H, m), 3.19 (2H, q, J=10.3 Hz), 2.95 (2H, d, J=11.9 Hz), 2.39-2.50 (2H, m), 1.82 (2H, dd, J=14.0, 3.2 Hz), 1.53-1.68 (2H, m). LC/MS (M+H)=400.36 expected, 400.0 observed.

Workup

  1. washThe resulting solids were washed in H2O
  2. filtrationcollected by filtration

Sources & evidence

ORD record
ord-368ebcdc386544be81ef5739d241a1dc
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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