Cesium carbonate → 3-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)benzaldehyde

HRID 576130Notes

Reaction equation

HRID 576130 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)=[O:2].Br[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([N:19]=[CH:20][N:21]=2)[CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:21]1[CH:20]=[N:19][N:17]2[CH:18]=[C:13]([C:5]3[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=3)[CH:1]=[O:2])[CH:14]=[CH:15][C:16]=12

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27343563-Formylphenylboronic acidHCID 115139346-Bromo-(1,2,4)triazolo(1,5-a)pyridine

Product 1

HCID 595803353-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)benzaldehydeYield 86%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a mixture of 3-formylphenylboronic acid (21.41 g, 143 mmol), 6-bromo-[1,2,4]triazolo[1,5-a]pyridine (28.27 g, 143 mmol) in DMSO (600 mL) and water (50 mL) was added Pd(dppf)Cl2 (5.83 g, 7.14 mmol) and Cs2CO3 (116 g, 357 mmol). The reaction temperature reached 45° C. after the addition. HPLC showed that starting materials were consumed after 15 min. The reaction was diluted with water (400 mL). The black precipitate was collected by filtration and dissolved in DCM (300 mL), and washed with brine (200 mL). The aqueous layer was back extracted with DCM (100 mL). The combined organic layers were filtered through a Celite pad and the filtrate was concentrated to give a black solid mixture. The product was recrystallized in methanol to give 3-([1,2,4]triazolo[1,5-a]pyridin-6-yl)benzaldehyde (27.4 g, 123 mmol, 86% yield) as a pale grey solid: m/z=224.0 [M+1]; 1H NMR (400 MHz, DMSO-D6) δ ppm 7.74 (t, J=7.68 Hz, 1H), 7.91-8.02 (m, 2H), 8.11 (dd, J=9.19, 1.89 Hz, 1H), 8.17 (d, J=7.81 Hz, 1H), 8.36 (s, 1H), 8.57 (s, 1H), 9.45 (s, 1H), 10.11 (s, 1H).

Workup

  1. customreached 45° C.
  2. additionafter the addition
  3. customwere consumed after 15 min
  4. additionThe reaction was diluted with water (400 mL)
  5. filtrationThe black precipitate was collected by filtration
  6. dissolutiondissolved in DCM (300 mL)
  7. washwashed with brine (200 mL)
  8. extractionThe aqueous layer was back extracted with DCM (100 mL)
  9. filtrationThe combined organic layers were filtered through a Celite pad
  10. concentrationthe filtrate was concentrated
  11. customto give a black solid mixture
  12. customThe product was recrystallized in methanol

Sources & evidence

ORD record
ord-2bae91c3f64d43ecbfc2fdc543eb9d25
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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