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Cesium carbonate → Toluene-4-sulfonic acid 4-[2-(4-chloro-phenyl)-4-oxo-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]-2-methoxy-phenyl ester

HRID 601524
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HRID 601524 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:17])[NH:12][CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1.Br[C:19]1[CH:24]=[CH:23][C:22]([O:25][S:26]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)(=[O:28])=[O:27])=[C:21]([O:36][CH3:37])[CH:20]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=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]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:11](=[O:17])[N:12]([C:19]4[CH:24]=[CH:23][C:22]([O:25][S:26]([C:29]5[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=5)(=[O:28])=[O:27])=[C:21]([O:36][CH3:37])[CH:20]=4)[CH2:13][CH2:14][C:15]=3[N:16]=2)=[CH:4][CH:3]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 575017522-(4-Chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-oneHCID 866292054-Bromo-2-methoxyphenyl 4-methylbenzene-1-sulfonate

생성물 1

HCID 57870236Toluene-4-sulfonic acid 4-[2-(4-chloro-phenyl)-4-oxo-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]-2-methoxy-phenyl ester
수율 60%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

Mix 2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (128 mg, 0.48 mmol), toluene-4-sulfonic acid 4-bromo-2-methoxy-phenyl ester (218 mg, 0.61 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17.2 mg, 0.030 mmol), Cs2CO3 (0.123 mg, 0.377 mmol) in dioxane (13 mL). Purge the solution with nitrogen for 30 min and then add tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (6.7 mg, 0.0073 mmol). Stir the mixture at reflux overnight, then cool to room temperature. Dilute the mixture with EtOAc (50 mL) and wash with water (2×30 mL) and brine (30 mL). Dry, filter and concentrate the organic solution and purify the residue by flash chromatography, using a linear gradient of 100% hexanes to 80% EtoAc/hexanes as eluent, to give the title compound as a light brown solid (155 mg, 60%). MS (ES+) 541.0 (M+1)+. 1H NMR (CDCl3): δ 7.92 (d, 2H, J=8.4 Hz), 7.78 (d, 2H, J=8.4 Hz), 7.44 (d, 2H, J=8.8 Hz), 7.31 (d, 2H, J=8.4 Hz), 7.17 (d, 1H, J=8.8 Hz), 6.96 (d, 1H, J=2.6 Hz), 6.82 (dd, 1H, J=8.6, 2.4 Hz), 4.11 (t, 2H, J=6.8 Hz), 3.57 (s, 3H), 3.28 (t, 2H, J=6.8 Hz), 2.44 (s, 3H).

후처리

  1. customPurge the solution with nitrogen for 30 min
  2. temperatureat reflux overnight
  3. washwash with water (2×30 mL) and brine (30 mL)
  4. customDry
  5. filtrationfilter
  6. concentrationconcentrate the organic solution
  7. custompurify the residue by flash chromatography

출처 및 근거

ORD 기록
ord-40fc9793b5224d79b718d05d1352515c
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07902356B2

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