Potassium Carbonate → 1-(2,3-difluoro-6-methoxybenzyl)-N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide

HRID 1753231Notes

Reaction equation

HRID 1753231 reaction equation
[F:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[NH:9][CH:8]=1)=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][C:24]1[C:29]([F:30])=[C:28]([F:31])[CH:27]=[CH:26][C:25]=1[O:32][CH3:33]>CN(C=O)C>[F:30][C:29]1[C:28]([F:31])=[CH:27][CH:26]=[C:25]([O:32][CH3:33])[C:24]=1[CH2:23][N:9]1[C:10]2[C:11](=[N:12][CH:13]=[CH:14][CH:15]=2)[C:7]([C:5]([NH:4][CH2:3][CH2:2][F:1])=[O:6])=[CH:8]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 49958612,3-Difluoro-6-methoxybenzyl bromideHCID 117818541N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide

Product 1

HCID 904667021-(2,3-difluoro-6-methoxybenzyl)-N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamideYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

See FIG. 17(a). In a 50 mL round-bottomed flask N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (0.1 g, 0.48 mmol) was DMF (10 mL) to give a colourless suspension. the reaction mixture was cooled to 0° C. and potassium carbonate (0.200 g, 1.45 mmol) and 2-(bromomethyl)-3,4-difluoro-1-methoxybenzene (0.114 g, 0.48 mmol) was added then the RM was stirred at 80° C. for 4 h. The reaction was monitored by LCMS. DMF was concentrated under vacuao, added water and extracted with DCM. The combined organic layer was washed with brine, dried over sodium sulphate, filtered and evaporated to give crude product. The crude material was purified on reverse phase preparative HPLC system to get 1-(2,3-difluoro-6-methoxybenzyl)-N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (0.060 g, 34.2%). ES+MS m/z: 364 (M+1) 1H NMR (DMSO-d6, 300 MHZ): δ ppm 8.90 (br. s., 1 H ), 8.50 (d, J=4.3 Hz, 1 H ), 8.02-8.15 (m, 2 H ), 7.30-7.52 (m, 2 H ), 6.92 (d, J=8.7 Hz, 1 H ), 5.53 (s, 2 H ), 4.63 (t, J=4.4 Hz, 1 H ), 4.47 (t, J=4.8 Hz, 1 H ), 3.86 (s, 3 H ), 3.74 (d, J=5.3 Hz, 1 H ), 3.65 (d, J=5.3 Hz, 1 H ).

Workup

  1. concentrationDMF was concentrated under vacuao
  2. additionadded water
  3. extractionextracted with DCM
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customto give crude product
  9. customThe crude material was purified on reverse phase preparative HPLC system

Sources & evidence

ORD record
ord-84a2754992134858b3781fc7d72fb7b0
Source dataset
uspto-grants-2015_10
Patent number
US09163020B2

Reaction notes

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