4-(Diethoxyphosphorylmethyl)pyridine → (E)-3-(2-(pyridin-4-yl)vinyl)-1H-indazole-6-carbonitrile

HRID 1615208Notes

Reaction equation

HRID 1615208 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7]P(=O)(OCC)OCC)=[CH:3][CH:2]=1.C(O[K])(C)(C)C.[CH:22]([C:24]1[C:32]2[C:27](=[CH:28][C:29]([C:33]#[N:34])=[CH:30][CH:31]=2)[NH:26][N:25]=1)=O>CN(C=O)C>[N:1]1[CH:2]=[CH:3][C:4](/[CH:7]=[CH:22]/[C:24]2[C:32]3[C:27](=[CH:28][C:29]([C:33]#[N:34])=[CH:30][CH:31]=3)[NH:26][N:25]=2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 100786024-(Diethoxyphosphorylmethyl)pyridineHCID 178418922HCID 178418922, compoundHCID 178509486HCID 178509486, compound

Product 1

HCID 66734432(E)-3-(2-(pyridin-4-yl)vinyl)-1H-indazole-6-carbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Diethyl pyridin-4-ylmethylphosphonate was redissolved in DMF (25 mL) and cooled to 0° C. tBuOK (3.36 g, 30 mmol) was added portion wise over 2 min and the reaction mixture turned dark brown red. After stirring for 2 min at 0° C., a solution of 3-formyl-1H-indazole-6-carbonitrile (1.71 g, 10 mmol) in DMF (15 mL) was added dropwise by pipette over 5 min. The resulting mixture was stirred for 40 min at 0° C. before quenching with ice, 2N HCl (20 mL) and H2O (20 mL). After stirring for 10 min at rt, the reaction mixture was carefully basified with sat. NaHCO3 to pH about 8 and copious amounts of yellow precipitate formed. The solid was collected by suction filtration and rinsed with H2O. After dying under high vacuum, 2.016 g (82%) of title compound was obtained as beige solid. 1H NMR (400 MHz, DMSO-d6) δ 13.90 (s, 1H, NH), 8.60-8.54 (m, 2H), 8.43 (d, J=8.0 Hz, 1H), 8.20 (s, 1H), 7.93 (d, J=16.0 Hz, 1H), 7.70 (d, J=4.0 Hz, 2H), 7.58 (d, J=8.0 Hz, 1H, partially overlapping with the doublet at 7.55 ppm), 7.55 (d, J=16.0 Hz, 1H, partially overlapping with the doublet at 7.58 ppm); MS ESI 250.0 [M+H]+, calcd for [C15H11N3O+H]+ 250.1.

Workup

  1. additionwas added portion wise over 2 min
  2. stirringThe resulting mixture was stirred for 40 min at 0° C.
  3. custombefore quenching with ice, 2N HCl (20 mL) and H2O (20 mL)
  4. stirringAfter stirring for 10 min at rt
  5. customformed
  6. filtrationThe solid was collected by suction filtration
  7. washrinsed with H2O

Sources & evidence

ORD record
ord-d4df4aea23be41158f49f1d746ad58a1
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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