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

HRID 1890761노트

반응식

HRID 1890761 반응식
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]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 58486430HCID 58486430, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9f8835368ba143b09314403810ccd57c
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507490B2

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