3-Fluorophenol → HCID 68765011, compound

HRID 387593

Reaction equation

HRID 387593 reaction equation
I[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)=[C:4]2[CH:10]=[N:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5]2=[N:6][CH:7]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C([O-])([O-])=O.[Cs+].[Cs+].[F:52][C:53]1[CH:54]=[C:55]([OH:59])[CH:56]=[CH:57][CH:58]=1>CN1C(=O)CCC1.O>[F:52][C:53]1[CH:54]=[C:55]([CH:56]=[CH:57][CH:58]=1)[O:59][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)=[C:4]2[CH:10]=[N:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 97433-FluorophenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 68758063tert-butyl 4-(5-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68765011HCID 68765011, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of tert-butyl 4-(5-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.100 g, 0.182 mmol, see Example 13), Cu(I)Cl (0.00901 g, 0.0910 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (0.00950 mL, 0.0455 mmol), Cs2CO3 (0.119 g, 0.364 mmol) and 3-fluorophenol (0.165 mL, 1.82 mmol) in NMP (2 mL) was stirred at 106° C. for 20 hours. The reaction was then cooled to room temperature, and H2O (5 mL) was added. The reaction mixture was then extracted with ethyl acetate (15 mL), washed with brine, and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 2.5:1) to give tert-butyl 4-(5-(3-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.020 g, 21%) as a solid. MS APCI (+) m/z 534.4 detected.

Workup

  1. extractionThe reaction mixture was then extracted with ethyl acetate (15 mL)
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of the solvent
  5. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 2.5:1)

Sources & evidence

ORD record
ord-4a14fafd26084d28840f43d2c916844a
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Linked notes

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