Sodium Carbonate → 5-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamine

HRID 83555ノート

反応式

HRID 83555 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](I)=[CH:11][C:10]([NH2:14])=[N:9]2)=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:10]([NH2:14])[CH:11]=2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:26])([F:27])[F:28])[CH:21]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 71287834HCID 71287834、化合物HCID 86680375HCID 86680375、化合物

生成物 1

HCID 712878655-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamine収率 115.7%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

To a solution of 1-(4-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (50 mg) prepared according to the same procedures as Preparation 18 in 1,2-dimethoxyethane (0.5 ml) were sequentially added 2-[3-chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (72 mg) prepared according to the same procedures as Preparation 22, a 2M aqueous solution of sodium carbonate (0.25 ml), tricyclohexylphosphine (9.3 mg) and palladium (II) acetate (3.7 mg) at room temperature, and the mixture was stirred at 100° C. for 2 hours. This reaction mixture was cooled to room temperature, filtered through Celite, and subjected to elution with ethyl acetate. The filtrate was extracted with ethyl acetate, the resulting organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1) to give the titled compound (79 mg).

後処理

  1. customprepared
  2. customaccording to the same procedures as Preparation 22
  3. filtrationfiltered through Celite
  4. washsubjected to elution with ethyl acetate
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washthe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1)

出典と根拠

ORDレコード
ord-7c484ac6613c4ebead43f7c570939f8f
出典データセット
uspto-grants-2014_09
特許番号
US08846746B2

反応ノート

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