Pyridine → 2-(3-Bromo-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-isoindole-1,3(2H)-dione

HRID 1991117Notes

Reaction equation

HRID 1991117 reaction equation
[Br:1]Br.[NH:3]1[C:7]2=[N:8][CH:9]=[C:10]([N:12]3[C:20](=[O:21])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])[CH:11]=[C:6]2[CH:5]=[CH:4]1.N1C=CC=CC=1.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[Br:1][C:5]1[C:6]2[C:7](=[N:8][CH:9]=[C:10]([N:12]3[C:13](=[O:22])[C:14]4[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:20]3=[O:21])[CH:11]=2)[NH:3][CH:4]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 24408BromineHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 591286702-(1H-Pyrrolo[2,3-b]pyridin-5-yl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 591286662-(3-Bromo-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-isoindole-1,3(2H)-dioneYield 100.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of Br2 (30.2 mg, 0.189 mmol) in CH2Cl2 (2.0 mL) was added dropwise over a period of 4 min. to a stirred and cooled (0° C.) solution of 41 (50 mg, 0.189 mmol) and pyridine (18.0 mg, 0.23 mmol) in CH2Cl2 (2 mL). After additional stirring at 0° C. for 26 min. the reaction mixture was treated with a 1:1 (v/v) solution of saturated aqueous NaHCO3 and saturated aqueous Na2S2O3. Stirring continued for 30 min at 0° C. and the organic phase was separated. The aqueous layer was extracted with CH2Cl2. The combined organic solutions were dried (MgSO4), concentrated and the residue was separated by LCMS (column LUNA 10 μ C18(2) 00G-4253-V0 250×50 mm) using water—MeCN (0.1% AcOH) as eluent (in gradient; flow 80 mL/min) to afford 42 (64.7 mg, quant.). 1H NMR (400 MHz; CDCl3+3 drops of CD3OD) δ 7.40 (s, 1H), 7.81 (dd, J=3.1, 5.4 Hz, 2H), 7.94 (d, J=2.3 Hz, 1H), 7.96 (dd, J=5.5, 3.1 Hz, 2H), 8.29 (d, J=2.3 Hz, 1H); MS (ES) m/z 383 (MH++MeCN).

Workup

  1. stirringAfter additional stirring at 0° C. for 26 min. the reaction mixture
  2. stirringStirring
  3. customthe organic phase was separated
  4. extractionThe aqueous layer was extracted with CH2Cl2
  5. dry with materialThe combined organic solutions were dried (MgSO4)
  6. concentrationconcentrated
  7. customthe residue was separated by LCMS (column LUNA 10 μ C18(2) 00G-4253-V0 250×50 mm)

Sources & evidence

ORD record
ord-890ba219fd664076a7ca35c7de29346f
Source dataset
uspto-grants-2010_01
Patent number
US07645769B2

Reaction notes

Loading…