6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one → 6-((4-chlorophenyl)ethynyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one

HRID 2059868ノート

反応式

HRID 2059868 の反応式
Cl[C:2]1[N:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=2)[C:4](=[O:22])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:28]#[C:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)CCC>CN(C=O)C.C(Cl)Cl.[Cu]I.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:36][C:33]1[CH:34]=[CH:35][C:30]([C:29]#[C:28][C:2]2[N:7]=[CH:6][N:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=3)[C:4](=[O:22])[CH:3]=2)=[CH:31][CH:32]=1

参加物

7

反応物 2

HCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-oneHCID 58580242Tributyl((4-chlorophenyl)ethynyl)stannane

生成物 1

HCID 469275036-((4-chlorophenyl)ethynyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one収率 30%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
55 °C

実験手順

A mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one Part A of Procedure 11 (30 mg, 0.092 mmol), tributyl((4-chlorophenyl)-ethynyl)stannane (79 mg, 0.185 mmol), copper (I) iodide (5.28 mg, 0.028 mmol), and palladiumtetrakis (16 mg, 0.014 mmol) in DMF (1 mL) was stirred under nitrogen at 55° C. for 3 hours. The reaction was cooled to RT, diluted with CH2Cl2, washed with water, sat. NaHCO3, dried (Na2SO4), and concentrated to afford the crude product. The residue was purified using ISCO flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient). The product was re-purified using HPLC (C18 column/10:90 to 90:10 MeOH—H2O) to afford the desired product 6-((4-chlorophenyl)ethynyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one J-2 (12.4 mg, 0.028 mmol, 30.0% yield) as a yellow solid. LC/MS 425 (M+H)+, tR 0.95 min (method 5); 1H NMR (400 MHz, CDCl3) δ 8.14-8.17 (1H, m), 7.55 (2H, d), 7.39 (2H, d), 7.01 (1H, d), 6.85-6.93 (2H, m), 6.75 (1H, s), 3.89 (3H, s), 3.88 (2H, s), 1.37 (6H, s).

後処理

  1. temperatureThe reaction was cooled to RT
  2. washwashed with water, sat. NaHCO3
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customto afford the crude product
  6. customThe residue was purified
  7. customThe product was re-purified

出典と根拠

ORDレコード
ord-aa4a699c74f843eeae1bacdc9a93fc22
出典データセット
uspto-grants-2012_10
特許番号
US08278316B2

反応ノート

読み込み中…