4-Ethynyl-1-methyl-1H-pyrazole → 3,5-dimethoxy-4-(4-methoxy-benzyloxy)-2-(1-methyl-1H-pyrazol-4-ylethynyl)pyridine

HRID 1258434Notes

Reaction equation

HRID 1258434 reaction equation
I[C:2]1[C:7]([O:8][CH3:9])=[C:6]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:5]([O:20][CH3:21])=[CH:4][N:3]=1.[C:22]([C:24]1[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=1)#[CH:23]>CC#N.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:9][O:8][C:7]1[C:2]([C:23]#[C:22][C:24]2[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=2)=[N:3][CH:4]=[C:5]([O:20][CH3:21])[C:6]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1

Participants

6

Reactant 2

HCID 511383214-Ethynyl-1-methyl-1H-pyrazoleHCID 592006432-Iodo-3,5-dimethoxy-4-(4-methoxy-benzyloxy)-pyridine

Product 1

HCID 686980513,5-dimethoxy-4-(4-methoxy-benzyloxy)-2-(1-methyl-1H-pyrazol-4-ylethynyl)pyridineYield 95%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 2-iodo-3,5-dimethoxy-4-(4-methoxy-benzyloxy)-pyridine (95 mg, 0.237 mmol) and 4-ethynyl-1-methyl-1H-pyrazole (30 mg, 0.283 mmol) in dry MeCN (1.5 ml) and NEt3 (0.5 ml) was added Pd(Ph3P)2Cl2 (12 mg, 7 mol %) and the reaction vessel was evacuated and backfilled with nitrogen three times. Copper (I) iodide (5 mg, 11 mol %) was added and the reaction mixture immediately became dark. Stirring was continued for 0.5 hours then the crude mixture was concentrated directly onto silica-gel under reduced pressure and the solid residue was purified by flash chromatography (silica-gel, eluted sequentially with EtOAc:hexanes, 2:1, 3:1, 1:0) to give the product as a white solid (85 mg, 95%). 1H—NMR (300 MHz, CDCl3) δ 7.98 (s, 1H), 7.66 (s, 1H), 7.57 (s, 1H), 7.34 (d, J=8.6 Hz, 2H), 6.86 (d, J=2H), 5.13 (s, 2H), 3.93 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H), 3.78 (s, 3H).

Workup

  1. customthe reaction vessel was evacuated
  2. additionCopper (I) iodide (5 mg, 11 mol %) was added
  3. concentrationthe crude mixture was concentrated directly onto silica-gel under reduced pressure
  4. customthe solid residue was purified by flash chromatography (silica-gel
  5. washeluted sequentially with EtOAc

Sources & evidence

ORD record
ord-4a65fdbe96a248abaebcb5092fb4a2a2
Source dataset
uspto-grants-2013_06
Patent number
US08466163B2

Reaction notes

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