(2,4-Dichlorophenyl)boronic acid → (1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol

HRID 1612109ノート

反応式

HRID 1612109 の反応式
Br[C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9].[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1B(O)O>C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9]

参加物

5

反応物 2

HCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 58583245(1R,2S)-1-[(5-bromo-3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol

生成物 1

HCID 58583246(1R,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol収率 133.7%

試薬・触媒・溶媒 2

HCID 241Benzene溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
80 °C

実験手順

A solution of (1R,2S)-1-[(5-bromo-3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol (1.48 g, 4.12 mmol) and 2,4-dichlorophenyl boronic acid (858 mg, 4.5 mmol) in benzene (41 mL) and 2M sodium carbonate (7 mL) was purged with nitrogen and treated with a single portion of bistriphenylphosphinepalladium(II)chloride (287 mg, 0.41 mmol). The resulting golden 2-phase solution was heated to 80° C. gradually darkening in color. After 16 hours, the reaction was cooled to room temperature, transferred to a separatory funnel, and washed with water (50 mL). The aqueous layer was extracted twice with ethyl acetate (75 mL) and the combined organics were washed once with brine (75 mL), dried over MgSO4, filtered, and concentrated to give 2.36 g of a brown syrup. This material was purified by biotage MPLC (90 g column, 20% ethyl acetate/heptane) to afford 1.25 g (71%) of the title compound as a tan solid. OAMS supporting ions at: ESI+ 428.0; HRMS (FAB) calcd for C23H23CL2N3O+H1 428.1296, found 428.1292.

後処理

  1. temperaturethe reaction was cooled to room temperature
  2. customtransferred to a separatory funnel
  3. washwashed with water (50 mL)
  4. extractionThe aqueous layer was extracted twice with ethyl acetate (75 mL)
  5. washthe combined organics were washed once with brine (75 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-d548687e575c4f478a194c14f0be1ac1
出典データセット
uspto-grants-2006_01
特許番号
US06992087B2

反応ノート

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