Cesium carbonate → N'-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-[(2R) 1,4-dioxan-2-ylmethyl]-N-methylsulfamide

HRID 1987102노트

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HRID 1987102 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:16]=[CH:15][C:9]3=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=[C:8]3[C:7](=[O:17])[C:6]=2[CH:18]=1.FC(F)(F)C([O-])=O.[O:26]1[CH2:31][CH2:30][O:29][CH2:28][C@H:27]1[CH2:32][N:33]([CH3:38])[S:34]([NH3+:37])(=[O:36])=[O:35].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.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O1CCOCC1>[Cl:14][C:12]1[CH:13]=[C:8]2[C:7](=[O:17])[C:6]3[CH:18]=[C:2]([NH:37][S:34]([N:33]([CH2:32][C@@H:27]4[CH2:28][O:29][CH2:30][CH2:31][O:26]4)[CH3:38])(=[O:35])=[O:36])[CH:3]=[CH:4][C:5]=3[CH:16]=[CH:15][C:9]2=[N:10][CH:11]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 159808187-Bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-B]pyridin-5-oneHCID 66972081{[((2R)1,4-dioxan-2-ylmethyl)(methyl)amino]sulfonyl}ammonium trifluoroacetate

생성물 1

HCID 53308833N'-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)-N-[(2R) 1,4-dioxan-2-ylmethyl]-N-methylsulfamide

시약·촉매·용매 2

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

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온도
95 °C

실험 절차

7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (1.41 g, 4.41 mmol), {[((2R)1,4-dioxan-2-ylmethyl)(methyl)amino]sulfonyl}ammonium trifluoroacetate (1.30 g, 4.01 mmol), tris(dibenzylideneacetone)dipalladium (0.183 g, 0.20 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene (0.347 g, 0.60 mmol), and cesium carbonate (3.91 g, 12.0 mmol) were combined in a dry flask. 50 mL dry dioxane was added and argon was bubbled through the solution for five minutes. The solution was stirred and heated to 95° C. After 2 hours, the solution was concentrated in vacuo, diluted with ethyl acetate, and washed with water and brine. The organic layer was isolated, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica chromatography (0-100% ethyl acetate/hexanes gradient) to afford the title compound. LRMS (APCI) calc'd for (C20H21ClN3O5S) [M+H]+, 450.1; found, 450.1.

후처리

  1. customargon was bubbled through the solution for five minutes
  2. concentrationthe solution was concentrated in vacuo
  3. additiondiluted with ethyl acetate
  4. washwashed with water and brine
  5. customThe organic layer was isolated
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by silica chromatography (0-100% ethyl acetate/hexanes gradient)

출처 및 근거

ORD 기록
ord-565bc2dafa38417b911cc0841cfb9c75
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550478B2

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