Potassium Carbonate → 8-benzyl-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773918

반응식

HRID 1773918 반응식
Br[C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:11]3)[CH:7]([O:22][CH:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:30](B1OC(C)(C)C(C)(C)O1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:30]([C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)=[CH:11]3)[CH:7]([O:22][CH:23]3[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 38649642-Benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 867040028-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

생성물 1

HCID 867040018-benzyl-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 70593637Toluene dioxane water용매

반응 조건

온도
95 °C

실험 절차

To a solution of 8-bromo-4-(1-methyl-piperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 231) (150 mg) in toluene/dioxane/water 10/1/1 (6 mL) in a screw-capped vial are added benzylboronic pinacol ester (151 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (50 mg) and potassium carbonate (137 mg). The vial is evacuated and filled with argon. The reaction mixture is stirred at 95° C. for 20 hours. Water is added to the reaction mixture, and the aqueous phase is extracted three times with dichloromethane. Pooled organic extracts are dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 23% (B) to 33% (B) in 10 minutes) to afford 8-benzyl-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 66° C.

후처리

  1. customThe vial is evacuated
  2. additionfilled with argon
  3. additionWater is added to the reaction mixture
  4. extractionthe aqueous phase is extracted three times with dichloromethane
  5. dry with materialPooled organic extracts are dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified by preparative HPLC-MS (Waters AutoPurification HPLC/MS System, Sunfire Prep C18 5 μm OBD 30×150 mm column, eluents: water/0.1% formic acid (A) and acetonitrile/0.1% formic acid (B), focus gradient from 23% (B) to 33% (B) in 10 minutes)

출처 및 근거

ORD 기록
ord-95641bda56d240d69101800a85022931
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255101B2

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