Diisopropylcarbodiimide → 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(5-phenyl-pyridin-2-yl)-propionamide

HRID 1093685Notes

Reaction equation

HRID 1093685 reaction equation
[C:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:14][C:15]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:16]=1[O:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24](=[O:29])[CH2:25][C:26](O)=[O:27])[CH2:20][CH2:19]1.CC(C)N=C=NC(C)C>C1COCC1>[Cl:14][C:15]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:16]=1[O:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24](=[O:29])[CH2:25][C:26]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:12][N:11]=2)=[O:27])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 1050975-Phenyl-2-pyridinamineHCID 578744413-[4-(2-Chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionic acid

Product 1

HCID 578744063-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(5-phenyl-pyridin-2-yl)-propionamideYield 18.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-phenyl-pyridin-2-ylamine (0.041 g, 0.00024 mole) in THF (3 mL) was added 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionic acid (0.08 g, 0.00025 mole) followed by DIC (0.036 g, 0.00028 mole). The mixture was heated to reflux for 3 hours, and then concentrated under educed pressure. The resulting residue was stirred with cold ether. The organic layers were removed by filtration and concentrated under reduced pressure to afford 0.021 g (18%) of 3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(5-phenyl-pyridin-2-yl)-propionamide. LC-MS purity: 468.14 (M+1)+, 98%, 1H NMR (DMSO-d6) δ 11.2 (bs, 1H), 8.2 (t, 2H), 8.0 (d, 1H), 7.4 (m, 4H), 7.1 (t, 1H), 6.6 (d, 2H), 4.6 (s, 1H), 4.0 (d, 1H), 3.7 (m, 1H), 3.6 (m, 3H), 2.1 (bs, 9H), 1.8 (t, 4H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 3 hours
  3. concentrationconcentrated under educed pressure
  4. customThe organic layers were removed by filtration
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a0f9661510dc407ba03d6a93bbf0f35b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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