Cesium carbonate → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

HRID 1926306Notes

Reaction equation

HRID 1926306 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[C:5](OS(C(F)(F)F)(=O)=O)[N:6]=[CH:7]2.CC1(C)C(C)(C)OB([C:29]2[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[C:5]([C:29]1[C:30]([NH2:35])=[N:31][CH:32]=[CH:33][CH:34]=1)[N:6]=[CH:7]2

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 438110672-Aminopyridine-3-boronic acid, pinacol esterHCID 86633140Trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester

Product 1

HCID 675212133-(5-Chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester (9.00 g, 27.4 mmol), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (8.42 g, 38.3 mmol), Pd(PPh3)4 (0.63 g, 2 mol %), and Cs2CO3 (20.5 g, 62.9 mmol) in dioxane/H2O (4:1, 300 mL) were heated under nitrogen at 100° C. for 16 h. Solvents were evaporated in vacuo, water (100 mL) was added to the residue, and the mixture was extracted with EtOAc (3×75 mL). The EtOAc extract was dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. It was purified by column chromatography on silica gel using EtOAc/Hexanes (1:3) to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=6.87 (brs, 2H), 6.81 (dd, J=8.7, 4.8 Hz, 1H), 7.18 (dd, J=9.3, 9.0 Hz, 1H), 7.22 (dd, J=8.1, 4.2 Hz, 1H), 7.99 (dd, J=7.5, 2.1 Hz, 1H), 8.15 (dd, J=6.8, 1.8 Hz, 1H), 8.13 (t, J=1.2 Hz, 1H), 9.56 (d, J=1.2 Hz, 1H).

Workup

  1. customSolvents were evaporated in vacuo, water (100 mL)
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with EtOAc (3×75 mL)
  4. extractionThe EtOAc extract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customIt was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-0d089d79a93540e1aa0842bb2b817e30
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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