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

HRID 1676326Notes

Reaction equation

HRID 1676326 reaction equation
[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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-983ba91aad74404388bb5124b6172bac
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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