4-Methylmorpholine → 6-(3-Fluorophenyl)-N-[1-(2,2,2-Trifluoroethyl)piperidin-4-Yl]pyridine-3-Carboxamide

HRID 602074Notes

Reaction equation

HRID 602074 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.CCN=C=NCCCN(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:42][C:43]([F:53])([F:52])[CH2:44][N:45]1[CH2:50][CH2:49][CH:48]([NH2:51])[CH2:47][CH2:46]1.CN1CCOCC1>CC(N(C)C)=O.O>[F:53][C:43]([F:42])([F:52])[CH2:44][N:45]1[CH2:50][CH2:49][CH:48]([NH2:51])[CH2:47][CH2:46]1.[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([NH:51][CH:48]3[CH2:49][CH2:50][N:45]([CH2:44][C:43]([F:53])([F:42])[F:52])[CH2:46][CH2:47]3)=[O:16])=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 162287221-(2,2,2-Trifluoroethyl)piperidin-4-amineHCID 23215488Edac edcHCID 247299726-(3-Fluorophenyl)nicotinic acid

Product 2

HCID 162287221-(2,2,2-Trifluoroethyl)piperidin-4-amineHCID 249910446-(3-Fluorophenyl)-N-[1-(2,2,2-Trifluoroethyl)piperidin-4-Yl]pyridine-3-CarboxamideYield 152.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

1-(2,2,2-Trifluoroethyl)piperidin-4-amine was synthesized as in steps a-c of Example 1. To a 250 mL round bottom flask containing 6-(3-fluorophenyl)pyridine-3-carboxylic acid (see Example 3, Step A)(2.01 g, 9.25 mmol ) in DMA (35 mL) was added EDAC/EDC*HCl(1.95 g, 10.2 mmol), HOBt (1.38 g, 10.2 mmol), 1-(2,2,2-trifluoroethyl)piperidin-4-amine (1.85 g, 10.2 mmol) and NMM (2.23 mL, 20.4). After stirring at room temperature for 2 hours the reaction mixture was diluted with water (100 mL) and the resulting solid filtered and dried to give the desired product (2.96 g). LCMS (ES+) 4.55 min (TIC, 90%; 1H NMR purity >95%); 1H NMR (400 MHz, DMSO-d6) □ ppm 1.60 (dq, J=11.84, 3.48 Hz, 2 H) 1.81 (d, J=10.62 Hz, 2H) 2.44 (t, J=11.16 Hz, 2H) 2.50 (br. s., 2H) 2.94 (d, J=11.53 Hz, 2H) 3.74-3.87 (m, 1H) 7.32 (dt, J=8.37, 2.29 Hz, 1H) 7.57 (q, 1H) 7.96 (d, J=10.43 Hz, 1H) 8.01 (d, J=7.69 Hz, 1H) 8.14 (d, J=8.24 Hz, 1H) 8.28 (dd, J=8.24, 2.20 Hz, 1H) 8.49 (d, J=7.50 Hz, 1H) 9.07 (d, J=1.83 Hz, 1H); MS(ES+) 382 (M+1); HRMS (TOF, ES+) calculated for C19H19F4N3O+H+: 382.1542; observed 382.1548.

Workup

  1. filtrationthe resulting solid filtered
  2. customdried

Sources & evidence

ORD record
ord-81f51e6f4f834c0e8972f1779cd2cf5d
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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