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

HRID 243329노트

반응식

HRID 243329 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]=[CH:33][C:34]=1[OH:35].[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]=[CH:33][C:34]([OH:35])=[C:29]([F:28])[CH:30]=3)[C:10]=12

참가 물질

7

반응물 3

HCID 25953Cesium fluorideHCID 23005361(3-Fluoro-4-hydroxyphenyl)boronic acidHCID 681579743-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 1361661304-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol수율 34.6%

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 (1.5 g, 3.2 mmol), 3-fluoro-4-hydroxyphenylboronic acid (0.6 g, 3.8 mmol), Pd(dppf)Cl2 (0.3 g) and CsF (1.0 g, 6.4 mmol) in DME (30 mL) and H2O (3 mL) was refluxed overnight. Then the mixture was cooled to room temperature, added H2O (50 mL) and extracted with EtOAc (30 mL×3). The combined organic layers were washed with brine and concentrated in vacuo. The residue was treated with CH2Cl2 and filtered to give 155 (500 mg, yield 34%) as a white solid. LCMS (ESI), M+H+=450.16. 1HNMR (400 MHz, DMSO) δ 5.875 (s, 2H), 7.046-7.120 (m, 2H), 7.175-7.200 (d, J=1.6 Hz, 1H), 7.242-7.307 (m, 3H), 7.432-7.472 (m, 5H), 7.687-7.708 (d, J=1.2 Hz, 1H), 8.335 (s, 1H)

후처리

  1. temperaturewas refluxed overnight
  2. extractionextracted with EtOAc (30 mL×3)
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated in vacuo
  5. additionThe residue was treated with CH2Cl2
  6. filtrationfiltered

출처 및 근거

ORD 기록
ord-1e0826944b4e45a2b1d406495c36873f
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653089B2

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