p-Fluoronitrobenzene → 1-(4-methoxybenzyl)-3-methyl-4-(4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridine

HRID 2241198Notes

Reaction equation

HRID 2241198 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][CH:15]=[C:16]([OH:17])[C:11]=3[C:10]([CH3:18])=[N:9]2)=[CH:5][CH:4]=1.F[C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(N(C)C)=O>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:22]4[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=4)=[C:11]3[C:10]([CH3:18])=[N:9]2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 9590p-FluoronitrobenzeneHCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 178490909HCID 178490909, compound

Product 1

HCID 685162851-(4-methoxybenzyl)-3-methyl-4-(4-nitrophenoxy)-1H-pyrazolo[3,4-b]pyridineYield 85.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 20 mL sealable tube under nitrogen was charged with 1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-ol (0.150 g, 0.557 mmol; prepared as in from Example 5, Step B), 1-fluoro-4-nitrobenzene (0.0786 g, 0.557 mmol), Cs2CO3 (0.272 g, 0.836 mmol), and DMA (4 mL). The reaction mixture was heated to 90° C. for 2 hours, then cooled to room temperature, diluted with water (10 mL) and extracted with EtOAc (15 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude was purified by Biotage 40S column eluting with Hexane/EtOAc 3:1, then EtOAc. Obtained the product (185 mg, 79%) as an off white solid. 1H NMR (CDCl3, 400 MHz) δ 8.39 (d, J=5.1 Hz, 1H), 8.32 (d, J=9.4 Hz, 1H), 7.34 (d, J=8.6 Hz, 1H), 7.26 (d, J=9.4 Hz, 1H), 6.84 (d, J=8.6 Hz, 1H), 6.40 (d, J=5.5 Hz, 1H), 3.77 (s, 3H), 2.58 (s, 3H). LRMS (esi pos) m/e 391 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc (15 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by Biotage 40S column
  7. washeluting with Hexane/EtOAc 3:1

Sources & evidence

ORD record
ord-77aae34413934a56958ff12cb4afb222
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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