Cesium carbonate → tert-Butyl 1-(6-(4-cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate

HRID 1890761ノート

反応式

HRID 1890761 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[C:4]([CH3:23])[C:3]=1[CH3:24].[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)#[N:26].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[C:25]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[N:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]3)=[C:4]([CH3:23])[C:3]=2[CH3:24])=[CH:29][CH:28]=1)#[N:26]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 58486430HCID 58486430、化合物

生成物 1

HCID 58486412tert-Butyl 1-(6-(4-cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate収率 94.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

Heat a mixture of tert-butyl 1-(6-chloro-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate (1.5 g, 4.23 mmol), 4-cyanophenylboronic acid (932 mg, 6.34 mmol), Cs2CO3 (5.51 g, 16.9 mmol) and (SP-4-1)-bis[bis(1,1-dimethylethyl)(4-methoxyphenyl)phosphine-κP]dichloro-palladium (29 mg, 0.042 mmol) in a mixture of 1,4-dioxane (30 mL) and H2O (10 mL) under N2 at 90° C. overnight. Partition the reaction mixture between EtOAc and H2O with dissolved NaHCO3. Separate the layers, and extract the aqueous layer with EtOAc. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a yellow solid (1.68 g, 94%). ES/MS m/z 422.2 (M+1).

後処理

  1. temperatureHeat
  2. customPartition the reaction mixture between EtOAc and H2O with dissolved NaHCO3
  3. customSeparate the layers
  4. extractionextract the aqueous layer with EtOAc
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-9f8835368ba143b09314403810ccd57c
出典データセット
uspto-grants-2013_08
特許番号
US08507490B2

反応ノート

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