(3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone → (3-(Benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol

HRID 926603Notes

Reaction equation

HRID 926603 reaction equation
[S:1]1[C:5]([CH2:6][C:7]2[C:8]([O:26][CH3:27])=[N:9][C:10]3[C:15]([C:16]=2[Cl:17])=[CH:14][C:13]([C:18]([C:20]2[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=2)=[O:19])=[CH:12][CH:11]=3)=[CH:4][C:3]2[CH:28]=[CH:29][CH:30]=[CH:31][C:2]1=2.[N:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[Mg]Br>C1COCC1>[S:1]1[C:5]([CH2:6][C:7]2[C:8]([O:26][CH3:27])=[N:9][C:10]3[C:15]([C:16]=2[Cl:17])=[CH:14][C:13]([C:18]([C:20]2[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=2)([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][N:32]=2)[OH:19])=[CH:12][CH:11]=3)=[CH:4][C:3]2[CH:28]=[CH:29][CH:30]=[CH:31][C:2]1=2

Participants

4

Reactant 2

HCID 118006347(3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 178419629HCID 178419629, compound

Product 1

HCID 118006238(3-(Benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LaCl3-2LiCl (0.6 M in THF, 0.78 mL, 0.47 mmol) was added dropwise by syringe to a solution of (3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (101.4 mg, 0.226 mmol, Intermediate 40: step b) in dry THF (2 mL). After 5 minutes, the solution was cooled in an ice bath and pyridin-2-ylmagnesium bromide (2.8 mL, 0.7 mmol) was added dropwise via syringe. The reaction was stirred for 3 hours, then quenched with saturated aqueous ammonium chloride and removed from the cold bath. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) followed by reverse-phase chromatography (acetonitrile/H2O+0.05% TFA). The isolated product fractions were basified with saturated aqueous sodium bicarbonate, extracted with DCM, dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.63-8.59 (m, 1H), 8.13 (d, J=2.0 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.71-7.60 (m, 4H), 7.49 (d, J=1.1 Hz, 1H), 7.30-7.18 (m, 4H), 7.08 (d, J=1.0 Hz, 1H), 6.32 (d, J=1.1 Hz, 1H), 4.50 (d, J=1.1 Hz, 2H), 4.13 (s, 3H), 3.41 (s, 3H); MS m/e 527.2 [M+H]+.

Workup

  1. temperaturethe solution was cooled in an ice bath
  2. customquenched with saturated aqueous ammonium chloride
  3. customremoved from the cold bath
  4. customThe mixture was partitioned between water and ethyl acetate
  5. extractionThe separated aqueous phase was further extracted with ethyl acetate
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM)
  10. extractionextracted with DCM
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-fe259d63c36445598ff776a6792ae1d4
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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