(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 623977ノート

反応式

HRID 623977 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-ea04d1681f5044388d76e37925b053ef
出典データセット
uspto-grants-2016_04
特許番号
US09303015B2

反応ノート

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