Dichloromethane → (4-Methoxy-3-[5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine

HRID 1593791

反応式

HRID 1593791 の反応式
Br[C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[O:5][CH:6]=1.B(OC(C)C)(OC(C)C)OC(C)C.C([Li])CCC.CCCCCC.I[C:40]1[CH:45]=[C:44]([N+:46]([O-])=O)[CH:43]=[CH:42][C:41]=1[O:49][CH3:50].ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:50][O:49][C:41]1[CH:42]=[CH:43][C:44]([NH2:46])=[CH:45][C:40]=1[C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[O:5][CH:6]=1

参加物

11

反応物 7

HCID 6344DichloromethaneHCID 8058HexaneHCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 948062-Iodo-1-methoxy-4-nitrobenzeneHCID 160991801-((4-Bromofuran-2-yl)methyl)-4-methylpiperazineHCID 178418339Butyllithium

生成物 1

HCID 16099182(4-Methoxy-3-[5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine収率 70.3%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a solution of 1-[(4-bromo-2-furyl)methyl]-4-methylpiperazine (1.43 g, 5.52 mmol) and tri-isopropyl borate (1.76 g, 9.38 mmol) in 20 mL of tetrahydrofuran at −78° C. was added 1.6 M n-butyl lithium in hexane (5.38 mL, 8.61 mmol) over 10 minutes. After stirring at −78° C. for 10 minutes, the temperature of the reaction mixture was allowed to rise to room temperature. Water (1.0 mL) was added and the solvents were removed in vacuo. The resultant intermediate boronic acid was dissolved in 20 mL of ethylene glycol dimethyl ether and 2-iodo-4-nitroanisole (1.06 mg, 4.25 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (87 mg, 0.11 mol) were added. A solution of 2.25 g of sodium carbonate in 6.5 mL of water was added and the resulting mixture was heated at reflux for 3 hours. The mixture was cooled to room temperature and partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography, eluting with a gradient of 5% methanol in dichloromethane to 10% methanol in dichloromethane to give 900 mg (70%) of (4-methoxy-3-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}phenyl)amine as a red oil.

後処理

  1. customto rise to room temperature
  2. customthe solvents were removed in vacuo
  3. dissolutionThe resultant intermediate boronic acid was dissolved in 20 mL of ethylene glycol dimethyl ether
  4. temperaturethe resulting mixture was heated
  5. temperatureat reflux for 3 hours
  6. temperatureThe mixture was cooled to room temperature
  7. custompartitioned between ethyl acetate and water
  8. extractionThe aqueous layer was further extracted with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash column chromatography
  14. washeluting with a gradient of 5% methanol in dichloromethane to 10% methanol in dichloromethane

出典と根拠

ORDレコード
ord-8aba0fcd93924d4fa7b09f7690661beb
出典データセット
uspto-grants-2007_11
特許番号
US07297795B2

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