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Sodium Carbonate → 4-[2-(cyclopropylmethoxy)-5-(pyridin-3-yl)phenyl]-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 930942
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HRID 930942 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)=[C:6]([C:8]2[C:9]3[CH:18]=[CH:17][N:16](S(C4C=CC(C)=CC=4)(=O)=O)[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O1CCOCC1.O.O.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]>[CH:31]1([CH2:30][O:29][C:5]2[CH:4]=[CH:3][C:2]([C:36]3[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=3)=[CH:7][C:6]=2[C:8]2[C:9]3[CH:18]=[CH:17][NH:16][C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH2:33][CH2:32]1
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참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27343783-Pyridinylboronic acidHCID 896575324-(5-bromo-2-(cyclopropylmethoxy)phenyl)-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

생성물 1

HCID 896562134-[2-(cyclopropylmethoxy)-5-(pyridin-3-yl)phenyl]-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one수율 75.1%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
120 °C

실험 절차

A suspension of Example 314b (100 mg, 0.190 mmol), pyridin-3-ylboronic acid (23.31 mg, 0.190 mmol), sodium carbonate (60.3 mg, 0.569 mmol), and tris(dibenzylideneacetone)-dipalladium(0) (15.48 mg, 0.019 mmol) in 4 mL dioxane-water (3:1) was heated under nitrogen under microwave conditions (Biotage Initiator) at 120° C. for 30 minutes. The reaction mixture was the treated with 1 mL aqueous 4 N NaOH and heated at 120° C. under microwave conditions again for 30 minutes. The mixture was diluted with water and extracted with ethyl acetate (2×), washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated and the residue was purified by flash chromatography (silica gel, 0-10% methanol/dichloromethane gradient) to give the title compound (53 mg, 75% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 11.95 (s, 1H), 8.90 (dd, J=2.4, 0.7 Hz, 1H), 8.56-8.49 (m, 1H), 8.07 (ddd, J=8.0, 2.4, 1.7 Hz, 1H), 7.71-7.64 (m, 2H), 7.45 (ddd, J=7.9, 4.8, 0.8 Hz, 1H), 7.34 (s, 1H), 7.26 (t, J=2.7 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 6.18 (dd, J=2.6, 2.2 Hz, 1H), 3.91 (d, J=6.7 Hz, 2H), 3.58 (s, 3H), 1.15-1.04 (m, 1H), 0.49-0.42 (m, 2H), 0.28-0.21 (m, 2H). MS (ESI+) m/z 372.2 (M+H)+.

후처리

  1. extractionextracted with ethyl acetate (2×)
  2. washwashed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by flash chromatography (silica gel, 0-10% methanol/dichloromethane gradient)

출처 및 근거

ORD 기록
ord-058d65bfe5d14a689a4412b32b44fff9
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09296741B2

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