Ethyl Acetate → 5-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile

HRID 506207ノート

反応式

HRID 506207 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]2[C:18]([C:19]#[N:20])=[CH:17][N:16]=[CH:15][C:14]=2I)[C:5]([CH3:11])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[Cl:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(OC(C)C)OC(C)C)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:14]2[CH:15]=[N:16][CH:17]=[C:18]([C:13]=2[NH:12][C:4]2[C:5]([CH3:11])=[C:6]3[C:10](=[C:2]([Cl:1])[CH:3]=2)[NH:9][CH:8]=[CH:7]3)[C:19]#[N:20])=[CH:28][CH:27]=1

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 684470354-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrileHCID 68466808Diisopropyl 4-(2-chloroethoxy)phenylboronate

生成物 1

HCID 684656455-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile収率 84.8%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

To a stirred solution of 4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]-5-iodonicotinonitrile (534 mg, 1.3 mmol) in DME (30 mL) was added diisopropyl 4-(2-chloroethoxy)phenylboronate (754 mg, 2.6 mmol), sodium carbonate solution (2.7 mL of 2M solution, 5.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (150 mg, 0.15 mmol) under nitrogen atmosphere and the reaction mixture was heated at 80° C. for 6 h and cooled to room temperature. Ethyl acetate was added and the organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue was purified by flash column chromatography (ethyl acetate/hexane) to give 5-[4-(2-chloroethoxy)phenyl]-4-[(7-chloro-4-methyl-1H-indol-5-yl)amino]nicotinonitrile as a yellow solid (482 mg, 84%). HPLC retention time: 10.7 min.(g) and MS: 437.2 (M+H).

後処理

  1. temperaturecooled to room temperature
  2. washthe organic phase was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-39d9238e5e2d45dd8f24f14d31a953a6
出典データセット
uspto-grants-2010_08
特許番号
US07781591B2

反応ノート

読み込み中…