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Cesium carbonate → 3-Methoxy-N-methyl-4-((5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide

HRID 1487602
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HRID 1487602 반응식
Cl[C:2]1[N:3]=[C:4]([O:25][CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[N:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:74][C:75]1[CH:84]=[CH:83][C:78]([C:79]([NH:81][CH3:82])=[O:80])=[CH:77][C:76]=1[O:85][CH3:86].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:86][O:85][C:76]1[CH:77]=[C:78]([CH:83]=[CH:84][C:75]=1[NH:74][C:2]1[N:3]=[C:4]([O:25][CH:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[C:6]=2[N:7]=1)[C:79]([NH:81][CH3:82])=[O:80]
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 867264362-Chloro-5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

생성물 1

HCID 86726437
3-Methoxy-N-methyl-4-((5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide
수율 49.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
150 °C

실험 절차

To a solution of 2-chloro-5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.2 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1.1 equiv) in 1,4-dioxane (0.1 M) was added cesium carbonate (3 equiv). The reaction mixtures were heated, with microwave irradiation, in a microwave reactor at 150° C. for 2 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in MeOH) in hexane) to give the title compound (49.1%% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.11 (s, 9H) 0.85-0.93 (m, 2H) 1.68-1.82 (m, 2H) 2.06-2.18 (m, 2H) 2.79 (d, J=4.30 Hz, 3H) 3.51-3.66 (m, 4H) 3.77-3.86 (m, 2H) 3.96 (s, 3H) 5.47-5.55 (m, 1H) 5.56 (s, 2H) 7.50-7.57 (m, 2H) 7.71-7.76 (m, 2H) 7.83 (s, 1H) 7.92 (s, 1H) 8.34 (q, J=4.43 Hz, 1H) 8.52-8.60 (m, 3H); MS (ESI) m/z 605.6 [M+1]+.

후처리

  1. customThe reaction mixtures
  2. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  3. washwashed with ethyl acetate
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialThe organic layer was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in MeOH) in hexane)

출처 및 근거

ORD 기록
ord-eda9b0b407984f6490aa409994eb5418
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09428509B2

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