(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (4-Chloro-2-(diethylamino)-3-phenoxyquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 623977Notes

Reaction equation

HRID 623977 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:6]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[C:5]2[Cl:24].C([Li])CCC.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]([C:39]2[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=2)=[O:38])=[CH:33][CH:32]=1>O1CCCC1>[Cl:24][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:37]([C:34]3[CH:35]=[CH:36][C:31]([Cl:30])=[CH:32][CH:33]=3)([C:39]3[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=3)[OH:38])[CH:3]=2)[N:8]=[C:7]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:6]=1[O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 867154626-bromo-4-chloro-N,N-diethyl-3-phenoxyquinolin-2-amine2×HCID 178418339Butyllithium

Product 1

HCID 74223742(4-Chloro-2-(diethylamino)-3-phenoxyquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-bromo-4-chloro-N,N-diethyl-3-phenoxyquinolin-2-amine (525 mg, 1.29 mmol, Intermediate 5, step d) in tetrahydrofuran (12 mL) at −78° C. was added n-butyllithium (1.6 M solution in hexanes, 1.2 mL, 1.94 mmol) dropwise over 1 minute and stirred at this temperature for 5 minutes. To the resulting dark red solution was added (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (428 mg, 1.94 mmol, Intermediate 1, step b) and stirred in an ice bath (0° C.) for 0.5 hours. The yellow-orange solution was quenched with water and diluted with EtOAc. The organic phase was separated, dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 5% MeOH-DCM), affording the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, J=2.02 Hz, 1H), 7.64-7.70 (m, 2H), 7.46 (dd, J=2.02, 9.09 Hz, 1H), 7.42 (d, J=9.09 Hz, 2H), 7.29-7.35 (m, 4H), 7.06 (t, J=7.33 Hz, 1H), 6.98 (s, 1H), 6.80 (d, J=7.58 Hz, 2H), 6.16 (d, J=1.01 Hz, 1H), 3.51 (q, J=7.07 Hz, 4H), 3.34 (br. s., 3H), 1.05 (t, J=7.07 Hz, 6H)); MS m/e 548.8 [M+H]+.

Workup

  1. stirringstirred in an ice bath (0° C.) for 0.5 hours
  2. customThe yellow-orange solution was quenched with water
  3. additiondiluted with EtOAc
  4. customThe organic phase was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (silica gel, 5% MeOH-DCM)

Sources & evidence

ORD record
ord-ea04d1681f5044388d76e37925b053ef
Source dataset
uspto-grants-2016_04
Patent number
US09303015B2

Reaction notes

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