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 2059868노트

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HRID 2059868 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
55 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-aa4a699c74f843eeae1bacdc9a93fc22
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278316B2

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