1-Methyl-1H-1,2,3-triazole → HCID 118005534, compound

HRID 1478518Notes

Reaction equation

HRID 1478518 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[N:3]1.[Li]CCCC.[Cl:12][C:13]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:21]([Cl:29])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:30]([C:32]3[N:36]([CH3:37])[C:35]([CH3:38])=[N:34][CH:33]=3)=[O:31])[CH:19]=2)[N:14]=1>C1COCC1>[Cl:12][C:13]1[C:22]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:21]([Cl:29])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:30]([C:32]3[N:36]([CH3:37])[C:35]([CH3:38])=[N:34][CH:33]=3)([C:6]3[N:2]([CH3:1])[N:3]=[N:4][CH:5]=3)[OH:31])[CH:19]=2)[N:14]=1

Participants

5

Reactant 3

HCID 1401191-Methyl-1H-1,2,3-triazoleHCID 118005559HCID 118005559, compound2×HCID 178418339Butyllithium

Product 1

HCID 118005534HCID 118005534, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-45 °C

Procedure

To a flask containing 1-methyl-1H-1,2,3-triazole (125 mg, 1.5 mmol) was added THF (10 mL) and the colorless solution was cooled to −45° C. Then, n-BuLi (2.5 M in hexanes, 0.6 mL, 1.5 mmol) was added affording a suspension. The suspension was stirred between −40° C. and −10° C. for 30 minutes, then a THF solution of (2,4-dichloro-3-phenylquinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (500 mg, 1.26 mmol, Intermediate 18: step b, in 5 mL THF) was introduced and the mixture was allowed to warm up to room temperature. After 1 hour, the reaction mixture was heated to 40° C. for 3 hours and then quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (3×50 mL) and then with DCM (3×50 mL). The individual organic portions were washed with brine, dried over MgSO4, filtered, combined and concentrated to dryness. Chromatography on silica gel (5% MeOH-DCM increasing to 10% MeOH) provided material which was re-purified by preparative TLC (5% 2 M-NH3-MeOH-EtOAc) to provide the title compound as light tan solid. 1H NMR (500 MHz, CDCl3) δ 8.45-8.36 (m, 1H), 7.94 (d, J=8.8 Hz, 1H), 7.66-7.46 (m, 4H), 7.46-7.30 (m, 2H), 7.01 (s, 1H), 5.94 (s, 1H), 3.91 (s, 3H), 3.34 (s, 3H), 2.17 (s, 3H). MS (ESI): mass calcd. for C24H20Cl2N6O, 478.1, m/z found 479.1 [M+H]+.

Workup

  1. customaffording a suspension
  2. temperatureto warm up to room temperature
  3. waitAfter 1 hour
  4. temperaturethe reaction mixture was heated to 40° C. for 3 hours
  5. customquenched with aqueous NH4Cl solution
  6. extractionThe aqueous portion was extracted with EtOAc (3×50 mL)
  7. washThe individual organic portions were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customChromatography on silica gel (5% MeOH-DCM increasing to 10% MeOH) provided material which
  12. customwas re-purified by preparative TLC (5% 2 M-NH3-MeOH-EtOAc)

Sources & evidence

ORD record
ord-42a2ba3e695445f0ae5df1baa53b1002
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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