Potassium Hydroxide → 2-(2-(1,5-naphthyridin-2-yl)ethyl)-8-bromo-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 1777789Notes

Reaction equation

HRID 1777789 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[N:4]=1)=[CH2:2].[Br:13][C:14]1[C:15]2[N:16]([C:20](=[O:23])[NH:21][N:22]=2)[CH:17]=[CH:18][CH:19]=1.[OH-].[K+]>CN1C(=O)CCC1.C(Cl)Cl>[N:4]1[C:5]2[C:10](=[N:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[CH:12][C:3]=1[CH2:1][CH2:2][N:21]1[C:20](=[O:23])[N:16]2[CH:17]=[CH:18][CH:19]=[C:14]([Br:13])[C:15]2=[N:22]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 571924222-Ethenyl-1,5-naphthyridineHCID 671876628-bromo-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 715716702-(2-(1,5-naphthyridin-2-yl)ethyl)-8-bromo-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 62%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

2-Vinyl-1,5-naphthyridine (10-2) (109 mg, 0.70 mmol) and triazolopyridinone 1-5 (150 mg, 0.70 mmol) were placed in a microwave vial and dissolved in NMP (1 mL). To the mixture was added catalytic powdered KOH (7.9 mg, 0.14 mmol), and the vial was capped and heated at 160° C. under microwave irradiation for 20 min. After cooling, the mixture was diluted with CH2Cl2 (100 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel flash column chromatography (40 g cartridge), eluting with 20-100% EtOAc/hexanes, then 1-10% EtOH/EtOAc. The fractions containing the desired product (10-3) were pooled, and after solvent removal in vacuo, 160 mg (62%) of a fluffy yellow solid were obtained. LC/MS: m/z (M+H)=370.0.

Workup

  1. customthe vial was capped
  2. temperatureAfter cooling
  3. washwashed with water (25 mL) and brine (25 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel flash column chromatography (40 g cartridge)
  8. washeluting with 20-100% EtOAc/hexanes
  9. additionThe fractions containing the desired product (10-3)
  10. customafter solvent removal in vacuo

Sources & evidence

ORD record
ord-d7c899f3858c43658eb5f1372c238a2e
Source dataset
uspto-grants-2016_02
Patent number
US09266881B2

Reaction notes

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