Diisopropylethylamine → HCID 24968689, compound

HRID 1666355Notes

Reaction equation

HRID 1666355 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:4][CH2:3]1.[C:26]1([C:32]2[N:33]=[CH:34][C:35]([NH:38][C:39](=O)[O:40]C3C=CC=CC=3)=[N:36][CH:37]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[C:26]1([C:32]2[N:33]=[CH:34][C:35]([NH:38][C:39]([N:2]3[CH2:7][CH2:6][C:5](=[CH:8][C:9]4[CH:25]=[CH:24][CH:23]=[C:11]([O:12][C:13]5[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][N:14]=5)[CH:10]=4)[CH2:4][CH2:3]3)=[O:40])=[N:36][CH:37]=2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9879110Phenyl 5-phenylpyrazin-2-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 24968689HCID 24968689, compoundYield 37.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 5-phenylpyrazin-2-ylcarbamate (0.291 g, 1.00 mmol) 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 purified by silica gel chromatography (10% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound (200 mg, 37%) as white crystals after trituration in diethyl ether. MS (APCI 10V) AP+ 532.25; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.50 (t, J=5.46 Hz, 2H) 6.37 (s, 1H) 6.69 (d, J=8.77 Hz, 1H) 7.01-7.03 (m, 2H) 7.10 (d, J=7.81 Hz, 1H) 7.19 (d, J=8.59, Hz, 1H) 7.35-7.39 (m, 2H) 7.43-7.47 (m, 2H) 8.02 (dd, J=7.03 Hz, 1.95 Hz, 2H) 8.17 (dd, J=8.78 Hz, 2.15 Hz, 1H) 8.53 (d, J=2.5 Hz, 1H) 8.85 (s, 1H) 9.04 (s, 1H) 9.63 (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 purified by silica gel chromatography (10% of the 1N NH3 in MeOH

Sources & evidence

ORD record
ord-14c9e289e34d417dbf0ec568b8465d1f
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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