Potassium Phosphate, Tribasic → 6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2079554노트

반응식

HRID 2079554 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:4]=2[CH:3]=1.[OH:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[OH:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[N:7]=[C:6]([C:8]#[N:9])[C:5]3[N:10]=[CH:11][N:12]([CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][O:14]4)[C:4]=3[CH:3]=2)=[CH:26][C:25]=1[C:33]([F:34])([F:35])[F:36]

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575354-(3-Hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acidHCID 592183456-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

생성물 1

HCID 576575386-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile수율 63%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.4 g), 4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acid (2.2 g), tris(dibenzylideneacetone)dipalladium (0.25 g), tricyclohexylphosphine (0.18 g) and potassium phosphate (2 g) were added to dioxane (20 ml) and water (6 ml) and the mixture was heated to reflux under nitrogen for two hours. The reaction mixture was diluted with EtOAc (200 mL), filtered through celite, and washed with water (150 mL). Organic layer was dried over sodium sulphate and solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using EtOAc:Heptane as eluant to yield 6-[4-(3-hydroxypropoxy)-3-(trifluoromethyl)-phenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.5 g).

후처리

  1. temperaturethe mixture was heated
  2. temperatureto reflux under nitrogen for two hours
  3. filtrationfiltered through celite
  4. washwashed with water (150 mL)
  5. dry with materialOrganic layer was dried over sodium sulphate and solvent
  6. customwas evaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-9e6c95fb6442430c9f919667ce5da0fe
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07932251B2

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