Cesium carbonate → N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]methanesulfonamide

HRID 2089014Notes

Reaction equation

HRID 2089014 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH:5]=[C:4](Cl)[N:3]=1.[CH3:18][S:19]([NH2:22])(=[O:21])=[O:20].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[OH-].[Na+]>O1CCOCC1.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][S:19]([CH3:18])(=[O:21])=[O:20])[CH:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH:7]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 87191335CID 87191335

Product 1

HCID 50939332N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]methanesulfonamideYield 5.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of Example 61a (0.130 g, 0.322 mmol), methanesulfonamide (0.046 g, 0.482 mmol), cesium carbonate (0.136 g, 0.418 mmol), palladium acetate (3.61 mg, 0.016 mmol), and Xantphos (0.014 g, 0.024 mmol) in dioxane (3 mL) and DMF (0.1 mL) was heated at 160° C. for 30 minutes in a Biotage microwave reactor. The mixture was concentrated. The residue was treated with EtOAc and washed with 20% brine. The emulsion of the organic layer was concentrated. The solid was suspended in dioxane (4 mL), treated with 20% sodium hydroxide (0.15 mL, 0.322 mmol), and heated at 50° C. for 3 hours. The reaction mixture was concentrated. The residue was treated with DMSO/MeOH and purified by reverse-phase HPLC as described in Example 56 to give the title compound (6.0 mg) as trifluoroacetic acid salts. 1H NMR (300 MHz, DMSO-d6) ppm 3.36 (s, 3H), 7.26 (dd, J=7.93, 4.76 Hz, 1H), 7.41 (d, J=0.79 Hz, 1H), 7.55 (d, J=1.19 Hz, 1H), 8.27-8.40 (m, 3H), 10.76 (s, 1H), 12.36 (s, 1H). MS (ESI+) m/z 322.8 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. additionThe residue was treated with EtOAc
  3. washwashed with 20% brine
  4. concentrationThe emulsion of the organic layer was concentrated
  5. concentrationThe reaction mixture was concentrated
  6. additionThe residue was treated with DMSO/MeOH
  7. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-24761616ade34dab8930f384b7cea55a
Source dataset
uspto-grants-2013_05
Patent number
US08435980B2

Reaction notes

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