Triethylamine → 4-(3-(5-(pent-4-ynyloxy)pyridin-2-yloxy)benzylidene)-N-(Pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666512Notes

Reaction equation

HRID 1666512 reaction equation
[CH2:1]([O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]=[C:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:15]=2)=[N:11][CH:12]=1)[CH2:2][CH2:3][C:4]#[CH:5].[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[N:28]=1.C(N(CC)CC)C>CS(C)=O.O>[CH2:1]([O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:15]=[C:16]([CH:17]=[CH:18][CH:19]=2)[CH:20]=[C:21]2[CH2:26][CH2:25][N:24]([C:34]([NH:33][C:29]3[N:28]=[N:27][CH:32]=[CH:31][CH:30]=3)=[O:35])[CH2:23][CH2:22]2)=[N:11][CH:12]=1)[CH2:2][CH2:3][C:4]#[CH:5]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 866239225-(Pent-4-ynyloxy)-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine

Product 1

HCID 249662024-(3-(5-(pent-4-ynyloxy)pyridin-2-yloxy)benzylidene)-N-(Pyridazin-3-yl)piperidine-1-carboxamideYield 64.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

5-(Pent-4-ynyloxy)-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine (0.26 g, 0.746 mmol) and phenyl pyridazin-3-ylcarbamate (0.16 g, 0.746 mmol) were dissolved in DMSO (3 mL) and triethylamine (0.3 mL) was added dropwise. The reaction was stirred for 12 h at RT. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel column chromatography (acetone:hexane, 2:5) to give the title compound (0.225 g, 64%). 1H NMR (500 MHz, CDCl3): δ 8.77 (s, 1H), 8.40 (s, 1H), 7.89 (s, 1H), 7.46 (t, J=4.5 Hz, 1H), 7.29 (m, 2H), 6.98 (d, J=7.5 Hz, 1H), 6.92 (m, 2H), 6.87 (d, J=8.75 Hz, 1H), 6.40 (s, 1H), 4.08 (t, J=5.75 Hz, 2H), 3.70 (m, 2H), 3.59 (m, 2H), 2.60 (d, J=5.2 Hz, 2H), 2.47 (m, 2H), 2.40 (t, J=6.6 Hz, 2H), 1.99 (m, 3H); 13C NMR (125 MHz, CDCl3): δ157.48, 156.60, 155.19, 151.80, 138.72, 137.46, 133.67, 129.42, 128.15, 126.84, 124.96, 124.59, 120.58, 118.38, 112.52, 83.14, 69.12, 67.25, 45.66, 44.64, 35.76, 29.13, 28.08, 15.06; m/z (470.2 MH+); HPLC: 97.8%.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. customThe residue was purified by silica gel column chromatography (acetone:hexane, 2:5)

Sources & evidence

ORD record
ord-5a12ecd7507744f7a719149f9668978a
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…