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Cesium carbonate → 3-[5-(4-Chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile

HRID 1024639
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HRID 1024639 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=4)[C:21]#[N:22])[C:11]=3[N:10]=[C:9]2[C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)=[CH:4][CH:3]=1.I[C:42]1[CH:47]=[N:46][CH:45]=[CH:44][N:43]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=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]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=4)[C:21]#[N:22])[C:11]=3[N:10]=[C:9]2[C:26]2[CH:27]=[CH:28][C:29]([C:42]3[CH:47]=[N:46][CH:45]=[CH:44][N:43]=3)=[CH:30][CH:31]=2)=[CH:6][CH:7]=1
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참가 물질

6

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HCID 10796Cesium carbonateHCID 642841IodopyrazineHCID 578994373-{5-(4-Chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl}-benzonitrile

생성물 1

HCID 578993843-[5-(4-Chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl}-benzonitrile (prepared as described in example 28, 3.6 g, 6.54 mmol) in N,N-dimethylformamide (70 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (2.0 g, 9.82 mmol), cesium carbonate (4.2 g, 13.09 mmol), Pd(dppf)2Cl2 (0.53 g, 0.654 mmol) is added and the resulted mixture is degassed with argon for 0.5 h The reaction mixture is then heated at 100° C. for 1.5 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3×). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford 3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyrazin-2-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile. 1H NMR (DMSO-d6, 400 MHz) δ 9.25 (s, 1H), 8.71 (m, 1H), 8.62 (m, 2H), 8.51 (m, 2H), 8.08 (d, 2H), 7.90 (m, 1H), 7.88 (m, 1H), 7.60 (d, 2H), 7.44 (m, 4H); LC-MS calculated for C28H16ClN7O (M+H+) 502.1, found 502.0.

후처리

  1. customthe resulted mixture is degassed with argon for 0.5 h The reaction mixture
  2. temperatureThe reaction mixture is cooled to rt
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by column chromatography

출처 및 근거

ORD 기록
ord-cd2c781fb14d40bab2dc1287016d6e62
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08722691B2

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