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Cesium carbonate → (S)-tert-Butyl (1-(6-(3,6-dihydro-2H-pyran-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

HRID 75303
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HRID 75303 반응식
Br[C:2]1[CH:3]=[C:4]2[N:20]([CH3:21])[CH:19]=[CH:18][C:5]2=[N:6][C:7]=1[C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9].[O:22]1[CH2:27][CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CCOC(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]>[O:22]1[CH2:23][CH:24]=[C:25]([C:2]2[CH:3]=[C:4]3[N:20]([CH3:21])[CH:19]=[CH:18][C:5]3=[N:6][C:7]=2[C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])[CH2:26][CH2:27]1
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8

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HCID 10796Cesium carbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 86707985(S)-tert-butyl (1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

생성물 1

HCID 86708002(S)-tert-Butyl (1-(6-(3,6-dihydro-2H-pyran-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

시약·촉매·용매 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 962Water용매
HCID 8857Ethyl Acetate용매
HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

To a 20 mL microwave vial were added (S)-tert-butyl (1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate (1 g, 2.8 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.890 g, 4.23 mmol), PdCl2(dppf) (0.207 g, 0.282 mmol) and cesium carbonate (1.84 g, 5.65 mmol) in dioxane (12 mL) and water (2 mL). The resulting brown suspension was heated in a microwave reactor at 90° C. on high absorbance for 1 hour. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was purified using silica gel column chromatography (12 g, 2:8 to 8:2 EtOAc/hexane) to give the title compound as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.99-1.13 (m, 9 H), 1.25-1.38 (m, 12 H), 3.74-3.97 (m, 7 H), 4.16-4.26 (m, 2H), 4.90-5.05 (m, 1 H), 5.68-5.77 (m, 1 H), 6.47-6.55 (m, 1 H), 6.76-6.87 (m, 1 H), 7.59 (s, 2 H); ESI-MS m/z [M+H]+ calc'd for C20H27N3O3, 358; found 358.

후처리

  1. washwashed with saturated aqueous NH4Cl (3×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified

출처 및 근거

ORD 기록
ord-9a3dc4d763594c358330656fed049f74
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08835420B2

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