Potassium Hydroxide → HCID 71573383, compound

HRID 1777778Notes

Reaction equation

HRID 1777778 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)=[CH2:2].[Br:13][C:14]1[N:19]2[C:20](=[O:23])[NH:21][N:22]=[C:18]2[CH:17]=[CH:16][CH:15]=1.[OH-].[K+]>CN1C(=O)CCC1.C(Cl)Cl>[Br:13][C:14]1[N:19]2[C:20](=[O:23])[N:21]([CH2:2][CH2:1][C:3]3[CH:12]=[CH:11][C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[N:4]=3)[N:22]=[C:18]2[CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 698752-VinylquinolineHCID 56777241HCID 56777241, compound

Product 1

HCID 71573383HCID 71573383, compoundYield 9.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

2-Vinylquinoline (1-2) (218 mg, 1.40 mmol) and triazolopyridinone 2-3 (250 mg, 1.17 mmol) were placed in a microwave vial and dissolved in NMP (2 mL). To the mixture was added catalytic powdered KOH (10 mg, 0.18 mmol), and the vial was capped and heated at 130° 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 25-100% EtOAc/hexanes. The fractions containing the desired product (2-4) were pooled, and after solvent removal in vacuo, 40 mg (9%) of a white solid were obtained. 1H NMR (400 MHz, CHCl3-d): δ 8.08 (d, J=8.4 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.69 (m, 1H), 7.50 (app t, J=7.6 Hz, 1H) 7.32 (d, J=8.8 Hz, 1H), 7.00 (d, J=11.6 Hz, 1H), 6.81 (dd, J=9.6, 7.2 Hz, 1H), 6.57 (d, J=7.2 Hz, 1H), 4.51 (t, J=7.2 Hz, 2H), 3.52 (t, J=7.2 Hz, 2H). HRMS (ES) 369.0346 (M+H) found, 369.0349 required.

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 25-100% EtOAc/hexanes
  9. additionThe fractions containing the desired product (2-4)
  10. customafter solvent removal in vacuo

Sources & evidence

ORD record
ord-af5c94621f5847bab347f49651ccc10f
Source dataset
uspto-grants-2016_02
Patent number
US09266881B2

Reaction notes

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