Cesium fluoride → 4-[4-Amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 1056945노트

반응식

HRID 1056945 반응식
[F-].[Cs+].Br[C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[O:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[F:22].[CH3:23][N:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:27]2=[CH:39][N:40]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:41]=[C:26]2[C:25]1=[O:50]>C(O)CCC.O.C(OCC)(=O)C.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.Cl[Pd]Cl>[NH2:8][C:7]1[CH:9]=[CH:10][C:4]([C:28]2[C:27]3[C:26](=[N:41][N:40]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:47])([CH3:49])[CH3:48])[CH:39]=3)[C:25](=[O:50])[N:24]([CH3:23])[CH:29]=2)=[C:5]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[C:6]=1[N+:11]([O-:13])=[O:12]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 1180939204-Bromo-3-(2,4-difluorophenoxy)-2-nitroanilineHCID 1317364506-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one

생성물 1

HCID 1234126994-[4-Amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one수율 50%

시약·촉매·용매 4

HCID 86647055di-tert-butyl(4-dimethylaminophenylphosphine) dichloropalladium(II)촉매HCID 2631-Butanol용매HCID 962Water용매2회HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A solution of 4-(di-tert-butylphosphino)-N,N-dimethylaniline-dichloropalladium (2:1) (22.3 mg, 0.0314 mmol), cesium fluoride (1.11 g, 7.34 mmol), 4-bromo-3-(2,4-difluorophenoxy)-2-nitroaniline (724 mg, 2.10 mmol), and 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (850 mg, 2.097 mmol) in 1-butanol (9.5 mL) and water (2.2 mL) was degassed with nitrogen for 5 min and heated at 100° C. for 2 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated and washed with brine, dried with magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (50% EtOAc/hexanes to 100% EtOAc) gave the desired product (0.57 g, 50%). LCMS calculated for C25H28F2N5O5Si (M+H)+: m/z=544.2. found: 544.1.

후처리

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification by flash column chromatography (50% EtOAc/hexanes to 100% EtOAc)

출처 및 근거

ORD 기록
ord-b82ce9447cc74328b366f921faf8847d
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09399640B2

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