Triphenylphosphine → 2-{5-[(4-fluorobenzyl)oxy]-1H-pyrazol-1-yl}pyridine-4-carbonitrile

HRID 878540Notes

Reaction equation

HRID 878540 reaction equation
[OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]O)=[CH:18][CH:17]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C(/N=N/C(N(C)C)=O)=O)C>C1COCC1>[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 680224-Fluorobenzylic alcoholHCID 5353800DiamideHCID 178510213HCID 178510213, compound

Product 1

HCID 867255122-{5-[(4-fluorobenzyl)oxy]-1H-pyrazol-1-yl}pyridine-4-carbonitrileYield 13.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile (185 mg, 0.99 mmol), 4-fluorobenzyl alcohol (188 mg, 1.49 mol), PPh3 (391 mg, 1.49 mmol) and THF (4 mL) cooled in an ice-water bath, TMAD (257 mg, 1.49 mmol) was added. The reaction mixture was stirred overnight at rt, filtered, and concentrated before purification by prep-HPLC to give the title compound (40 mg, 13%). 1H NMR (400 MHz, CDCl3): δ 5.14 (2H, s), 5.68 (1H, s), 7.00-7.05 (2H, m), 7.33-7.36 (3H, m), 7.52 (1H, s), 7.96 (1H, s), 8.64 (1H, s). [M+H] Calc'd for C16H11FN4O, 295; Found, 295.

Workup

  1. temperaturecooled in an ice-water bath
  2. filtrationfiltered
  3. concentrationconcentrated before purification by prep-HPLC

Sources & evidence

ORD record
ord-0d2109647dfa4964953bc4a768a9ee2e
Source dataset
uspto-grants-2015_03
Patent number
US08987461B2

Reaction notes

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