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Dichloromethane → (2',4'-Difluoro-biphenyl-4-yl)-(8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]oct-3-yl)-methanone

HRID 1619221
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HRID 1619221 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:16][CH:15]3[N:17]([C:18]4[N:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[CH:12]([CH2:13][CH2:14]3)[CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1B(O)O.ClCCl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.[OH-].[Na+].C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].O>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:11][CH:12]3[N:17]([C:18]4[N:19]=[CH:20][CH:21]=[CH:22][N:23]=4)[CH:15]([CH2:14][CH2:13]3)[CH2:16]2)=[O:9])=[CH:4][CH:3]=1
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참가 물질

9

반응물 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27343342,4-Difluorophenylboronic acidHCID 68699864(4-Bromo-phenyl)-(8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]oct-3-yl)-methanone

생성물 1

HCID 58754894(2',4'-Difluoro-biphenyl-4-yl)-(8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]oct-3-yl)-methanone수율 19%

시약·촉매·용매 4

HCID 178477754HCID 178477754, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 14798Sodium Hydroxide용매

실험 절차

A solution of (4-bromo-phenyl)-(8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]oct-3-yl)-methanone (250 mg, 0.92 mmol), 2,4-di-fluoro-phenylboronic acid (290 mg, 1.84 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (67 mg, 0.092 mmol), K3PO4(390 mg, 1.84 mmol), 2-dimethoxy-ethane (5 ml) and water (1.6 ml) was stirred at 80° C. for one hour. The reaction mixture was diluted with ethyl acetate and 1N NaOH solution. The organic layer was dried by MgSO4 and concentrated. ISCO was used for purification, and the product was obtained as a white solid (2′,4′-difluoro-biphenyl-4-yl)-(8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]oct-3-yl)-methanone (69.6 mg, 19%). MS (M+1)=406. 1H NMR (CDCl3) 8.34 (d, J=12 Hz 2H), 8.00 (d, J=21 Hz 2H), 7.62 (dd, J=19 Hz, 4 Hz, 2H), 7.45 (m, 1H), 6.99 (m, 2H), 6.52 (t, J=12 Hz, 1H), 4.90 (m, 2H), 4.00 (m, 1H), 2.25 (m, 2H), 2.12 (m, 2H), 2.02 (m, 2H), 1.78 (m, 2H).

후처리

  1. dry with materialThe organic layer was dried by MgSO4
  2. concentrationconcentrated
  3. customISCO was used for purification

출처 및 근거

ORD 기록
ord-4c40d4c7db8042dba9af2fbf216658be
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08772291B2

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