Toluene → 4-(7-(6-chloropyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide

HRID 1676326노트

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HRID 1676326 반응식
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)=[O:4].[Cl:14][C:15]1[N:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]3[CH:28]=[C:29](I)[S:30][C:23]=23)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>C(Cl)Cl.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[Cl:14][C:15]1[N:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]3[CH:28]=[C:29]([C:8]4[CH:9]=[CH:10][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:6][CH:7]=4)[S:30][C:23]=23)=[CH:17][CH:16]=1

참가 물질

9

반응물 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 866146527-(6-Chloropyridin-3-yloxy)-2-iodothieno[3,2-b]pyridine

생성물 1

HCID 589494324-(7-(6-chloropyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide수율 65.2%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 6344Dichloromethane용매

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온도
85 °C

실험 절차

A stirred mixture of 4-(methylcarbamoyl)phenylboronic acid (0.112 g, 0.625 mmol), 7-(6-chloropyridin-3-yloxy)-2-iodothieno[3,2-b]pyridine (0.194 g, 0.50 mmol), cesium carbonate (0.244 g, 0.750 mmol), toluene (4 mL) and EtOH (1 mL) was sparged with nitrogen for 5 minutes and then Pd(PPh3)4 (0.0347 g, 0.0300 mmol) was added. The reaction was heated to 85° C. for 5 hours in a sealed vessel. The mixture was diluted with DCM (20 mL) and water (20 mL). The phases were separated, and the organic was dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by preparative TLC (2 mm thickness, Rf=0.36) eluting with 10% MeOH/CHCl3. The product was obtained as a solid (129 mg, 59%). HPLC: 98% purity (220 nm); LRMS (ESI+): 97% purity, 220 nm, m/z 396 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J=6 Hz, 1H), 8.36 (d, J=3 Hz, 1H), 7.85 (m, 2H), 7.79 (m, 3H), 7.53 (d, J=9 Hz, 1H), 7.44 (d, J=9 Hz, 1H), 6.59 (d, J=6 Hz, 1H), 6.41 (br d, J=5 Hz, 1H), 3.05 (d, J=5 Hz, 3H).

후처리

  1. customwas sparged with nitrogen for 5 minutes
  2. customThe phases were separated
  3. dry with materialthe organic was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by preparative TLC (2 mm thickness, Rf=0.36)
  7. washeluting with 10% MeOH/CHCl3

출처 및 근거

ORD 기록
ord-983ba91aad74404388bb5124b6172bac
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003662B2

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