Tetrahydrofuran → HCID 118006303, compound

HRID 926611Notes

Reaction equation

HRID 926611 reaction equation
[N:1]1([C:6]2[CH:34]=[CH:33][C:9]([CH2:10][C:11]3[C:12]([C:31]#[N:32])=[N:13][C:14]4[C:19]([C:20]=3[C:21]#[N:22])=[CH:18][C:17]([C:23]([C:25]3[N:29]([CH3:30])[CH:28]=[N:27][CH:26]=3)=[O:24])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([Mg]Br)=[CH:38][CH:37]=1.[CH2:44]1COCC1>C(OCC)C>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([CH2:10][C:11]3[C:12]([C:31]#[N:32])=[N:13][C:14]4[C:19]([C:20]=3[C:21]#[N:22])=[CH:18][C:17]([C:23]([C:39]3[CH:40]=[CH:41][C:36]([Cl:35])=[CH:37][CH:38]=3)([OH:24])[C:25]3[N:29]([CH3:30])[CH:28]=[N:27][CH:26]=3)=[CH:16][C:15]=4[CH3:44])=[CH:33][CH:34]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 118006217HCID 118006217, compound2×HCID 178478191HCID 178478191, compound

Product 1

HCID 118006303HCID 118006303, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of LaCl3-2LiCl in THF (0.36 mL, 0.22 mmol, 0.6 M in THF) was added to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-(1-methyl-1H-imidazole-5-carbonyl)quinoline-2,4-dicarbonitrile (50 mg, 0.08 mmol, Intermediate 14: step e) in THF (1.8 mL) at room temperature. After 15 minutes of stirring, a solution of 4-chlorophenyl magnesium bromide (0.32 mL, 0.32 mmol) in diethylether was added dropwise at 0° C. After stirring for 30 minutes, the reaction mixture was quenched with a saturated aqueous solution of NH4Cl and the mixture was partitioned between water and DCM. The layers were separated and the aqueous phase was further extracted with DCM. The organic layers were combined, washed with saturated aqueous NaCl solution, dried (MgSO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-7% MeOH-DCM) to provide the title compound. MS m/e 570.3 (M+H)+.

Workup

  1. stirringAfter stirring for 30 minutes
  2. customthe reaction mixture was quenched with a saturated aqueous solution of NH4Cl
  3. customthe mixture was partitioned between water and DCM
  4. customThe layers were separated
  5. extractionthe aqueous phase was further extracted with DCM
  6. washwashed with saturated aqueous NaCl solution
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude product was purified by flash column chromatography (silica gel, 0-7% MeOH-DCM)

Sources & evidence

ORD record
ord-f2d2743f70f84358b72e54094030f321
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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