Dimethyl Sulfoxide → N-(6-methoxypyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666358Notes

Reaction equation

HRID 1666358 reaction equation
Cl.N1C[CH2:6][C:5](=[C:8]2[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=3)[CH:9]2C)CC1.[CH3:26][O:27][C:28]1[N:33]=[C:32]([NH:34]C(=O)OC2C=CC=CC=2)[CH:31]=[N:30][CH:29]=1.[CH:44]([N:47]([CH:50]([CH3:52])C)[CH2:48][CH3:49])(C)C.CS(C)=[O:55]>>[CH3:26][O:27][C:28]1[N:33]=[C:32]([NH:34][C:44]([N:47]2[CH2:48][CH2:49][C:6](=[CH:5][C:8]3[CH:24]=[CH:23][CH:22]=[C:10]([O:11][C:12]4[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][N:13]=4)[CH:9]=3)[CH2:52][CH2:50]2)=[O:55])[CH:31]=[N:30][CH:29]=1

Participants

5

Reactant 4

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 66875760Phenyl (6-methoxypyrazin-2-yl)carbamateHCID 668763562-(3-Piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride

Product 1

HCID 24963360N-(6-methoxypyrazin-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideYield 69%

Conditions

Temperature
60 °C

Procedure

A solution of 2-(3-piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 6-methoxypyrazin-2-ylcarbamate (0.245 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and heated to 60° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was crystallized in a 1:1 mix of hexanes and ethyl ether to afford the title compound (310 mg, 69%) as white crystals. MS (APCI 10 V) AP+ 486.20; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.33 (t, J=5.46 Hz, 2H) 2.44 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.55 (t, J=5.46 Hz, 2H) 3.86 (s, 3H) 6.37 (s, 1H) 7.02-7.04 (m, 2H) 7.10 (d, J=7.62 Hz, 1H) 7.20 (d, J=8.60, Hz, 1H) 7.38 (t, J=8.77 Hz, 1H) 7.81 (s, 1H) 8.20 (dd, J=8.59 Hz, 2.14 Hz, 1H) 8.55 (s, 1H) 8.58 (s, 1H) 9.25 (s, 1H).

Workup

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was crystallized in a 1:1
  9. additionmix of hexanes and ethyl ether

Sources & evidence

ORD record
ord-352ce4750d254ea3a9067945ebb4aee7
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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