2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 1-methyl-2-{[1-(2-oxo-1{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4']bipyrimidinyl-6-one

HRID 1468781

반응식

HRID 1468781 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:19])[O:8][CH2:7][C:6]=2[CH:20]=1.[CH3:21][N:22]1[C:27](=[O:28])[CH:26]=[C:25]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][N:30]=2)[N:24]=[C:23]1[O:35][CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:21][N:22]1[C:27](=[O:28])[CH:26]=[C:25]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][N:30]=2)[N:24]=[C:23]1[O:35][CH:36]1[CH2:41][CH2:40][N:39]([C:2]2[CH:3]=[CH:4][C:5]3[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:19])[O:8][CH2:7][C:6]=3[CH:20]=2)[CH2:38][CH2:37]1

참가 물질

7

반응물 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 679776501-methyl-2-(piperidin-4-yloxy)-1H-[4,4']bipyrimidinyl-6-oneHCID 679776606-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-2-one

생성물 1

HCID 679776661-methyl-2-{[1-(2-oxo-1{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4']bipyrimidinyl-6-one수율 11.2%

시약·촉매·용매 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)촉매HCID 1140Toluene용매

반응 조건

온도
150 °C

실험 절차

To a mixture of 6-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-2-one (620 mg, 1.7 mmol), 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one (500 mg, 1.7 mmol), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (72 mg, 70 μmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (130 mg, 0.28 mmol) in toluene (3.5 ml) was added sodium tert-butoxide (250 mg, 2.6 mmol) under nitrogen atmosphere. The mixture was stirred at 150° C. for 30 minutes utilizing Biotage microwave reactor. The mixture was filtered through a pad of Celite and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent; ethyl acetate) to afford 1-methyl-2-{[1-(2-oxo-1{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4′]bipyrimidinyl-6-one as a pale yellow solid (110 mg, 0.19 mmol, 11%).

후처리

  1. filtrationThe mixture was filtered through a pad of Celite
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by silica gel column chromatography (eluent; ethyl acetate)

출처 및 근거

ORD 기록
ord-53255b1933f84c2390bf4f8436f431b1
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006232B2

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