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 243327노트

반응식

HRID 243327 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-0dd9f859ec344753b9598a6c2a5d30f4
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653089B2

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