Isopropyl iodide → 3-[4-(benzyloxy)phenyl]-6-chloro-1-(1-methylethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 82654

반응식

HRID 82654 반응식
Cl[C:2]1[C:7]([NH:8][C:9](=[O:15])OC(C)(C)C)=[CH:6][C:5]([Cl:16])=[CH:4][N:3]=1.Cl.[CH2:18]([O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[CH3:33][C:34]1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2[C:35]1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].IC(C)C.[H-].[Na+].[Cl-].[Cl-].[Ca+2]>C1(C)C=CC=CC=1.CN(C=O)C.CO.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].CC(O)C>[CH2:18]([O:25][C:26]1[CH:27]=[CH:28][C:29]([N:30]2[C:2]3=[N:3][CH:4]=[C:5]([Cl:16])[CH:6]=[C:7]3[N:8]([CH:34]([CH3:35])[CH3:33])[C:9]2=[O:15])=[CH:31][CH:32]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

참가 물질

13

반응물 7

HCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27238314-Benzyloxyaniline hydrochlorideHCID 5284359Calcium ChlorideHCID 23676156Sodium t-butoxideHCID 86660673Tert-butyl 2,5-dichloropyridin-3-ylcarbamate

생성물 1

HCID 585775533-[4-(benzyloxy)phenyl]-6-chloro-1-(1-methylethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one수율 62.4%

시약·촉매·용매 5

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 887Methanol용매HCID 1140Toluene용매HCID 3776Isopropanol용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

Di-tert-butyl dicarbonate (17.05 mL) was added to a solution of 2,5-dichloropyridin-3-amine (11.4 g) and NaHMDS (81 mL) in THF(dry) (200 mL) at 0° C. The mixture was stirred at 0° C. under a dry atmosphere for 1 h. The mixture was neutralized with 1N HCl at 0° C. and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-20% EtOAc in hexane) to give tert-butyl 2,5-dichloropyridin-3-ylcarbamate (15.6 g) as colorless oil. The mixture of tert-butyl 2,5-dichloropyridin-3-ylcarbamate (7.5 g), 4-benzyloxyaniline hydrochloride (10.08 g), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (1.319 g), Pd2(dba)3 (1.044 g) and sodium tert-butoxide (6.57 g) in toluene (160 ml)-2-propanol (40.0 mL) was stirred at 100° C. under Ar overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane) to give intermediate. To the intermediate in DMF (100 ml) were added 2-iodopropane (5.69 mL) and NaH (2.280 g), and the mixture was stirred at room temperature under a dry atmosphere (CaCl2 tube) for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane) to give 3-[4-(benzyloxy)phenyl]-6-chloro-1-(1-methylethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (560 mg) as a colorless solid.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane)
  3. customto give intermediate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-41658c151aff4cf29976d413538edc36
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846713B2

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