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 1056945ノート

反応式

HRID 1056945 の反応式
[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]

参加物

8

反応物 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

生成物 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-one収率 50%

試薬・触媒・溶媒 4

HCID 86647055di-tert-butyl(4-dimethylaminophenylphosphine) dichloropalladium(II)触媒HCID 2631-Butanol溶媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b82ce9447cc74328b366f921faf8847d
出典データセット
uspto-grants-2016_07
特許番号
US09399640B2

反応ノート

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