Cesium fluoride → 3-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenol

HRID 243327ノート

反応式

HRID 243327 の反応式
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH2:12][C:13]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:16]3[CH:24]=[CH:25][CH:26]=[CH:27][C:15]=3[N:14]=2)[N:3]=1.[F:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([OH:35])[CH:34]=1.[F-].[Cs+]>COCCOC.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]>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:12][C:13]3[N:17]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:16]4[CH:24]=[CH:25][CH:26]=[CH:27][C:15]=4[N:14]=3)[N:3]=[C:2]([C:31]3[CH:32]=[C:33]([OH:35])[CH:34]=[C:29]([F:28])[CH:30]=3)[C:10]=12

参加物

7

反応物 3

HCID 25953Cesium fluorideHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 681579743-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 681581243-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenol収率 31.1%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

実験手順

A mixture of 3-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 141 (1.0 g, 2.14 mmol), 3-fluoro-5-hydroxyphenylboronic acid (0.4 g, 2.56 mmol), Pd(dppf)Cl2 (0.2 g) and CsF (0.65 g, 4.3 mmol) in DME (20 mL) and H2O (2 mL) was refluxed overnight. Then the mixture was cooled to room temperature, added H2O (50 mL) and extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and then concentrated in vacuo. The residue was treated with CH2Cl2 and filtered to give 153 (300 mg, yield 31%) as a grey solid. LCMS (ESI), M+H+=450.16. 1HNMR (400 MHz, DMSO) δ 5.795 (s, 2H), 6.606-6.633 (d, J=10.8 Hz, 1H), 6.720-6.724 (d, J=8.8 Hz, 1H), 6.800 (s, 2H), 7.065-7.083 (d, J=7.2 Hz, 1H), 7.213-7.260 (m, 2H), 7.400 (s, 5H), 7.657-7.676 (d, J=7.6 Hz, 1H), 8.119 (s, 1H), 10.139 (s, 1H)

後処理

  1. temperaturewas refluxed overnight
  2. extractionextracted with EtOAc (20 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. additionThe residue was treated with CH2Cl2
  7. filtrationfiltered

出典と根拠

ORDレコード
ord-0dd9f859ec344753b9598a6c2a5d30f4
出典データセット
uspto-grants-2014_02
特許番号
US08653089B2

反応ノート

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