Sodium Carbonate → 2,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 1865670Notes

Reaction equation

HRID 1865670 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1.[F:35][C:36]1[C:46]([F:47])=[CH:45][C:44](I)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39].C(=O)([O-])[O-].[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C(#N)C>[F:35][C:36]1[C:46]([F:47])=[CH:45][C:44]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])[C:12]3=[N:13][CH:14]=2)=[CH:43][C:37]=1[C:38]([N:40]([CH3:42])[CH3:41])=[O:39]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 579757722,3-difluoro-5-iodo-N,N-dimethyl-benzamideHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 579757282,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamideYield 68%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (3.1 g, 6.43 mmol), 2,3-difluoro-5-iodo-N,N-dimethyl-benzamide (2 g, 6.43 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)-dichloride dichlormethane adduct (262 mg, 0.32 mmol) in acetonitrile (14 mL) and aqueous solution of sodium carbonate (2M, 6.5 mL) was irradiated in a Personal Chemistry Optimizer at 100° C. for 15 min. Sodium sulfate was added to the crude reaction mixture and the solids were filtered over Celite. The solids were washed with acetonitrile and the combined filtrate was concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded 1.23 g (4.37 mmol, 68%) of 2,3-difluoro-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J=2.5 Hz, 1H), 8.46 (d, J=2 Hz, 1H), 8.02 (ddd, J=12 Hz, J2=10 Hz, J3=2.5 Hz, 1H), 7.67 (m, 1H), 7.61 (dd, J1=8 Hz, J2=1.5 Hz, 1H), 7.49 (m, 1H), 7.23 (d, J=8 Hz, 1H), 7.10 (td, J=8 Hz, J2=1 Hz, 1H), 5.84 (s, 2H), 3.81 (s, 3H), 3.68 (t, J=8 Hz, 2H), 3.02 (s, 3H), 2.91 (s, 3H), 0.85 (t, J=8 Hz, 2H), −0.09 (s, 9H). MS: m/z 539 [MH+]

Workup

  1. customwas irradiated in a Personal Chemistry Optimizer at 100° C. for 15 min
  2. customreaction mixture
  3. filtrationthe solids were filtered over Celite
  4. washThe solids were washed with acetonitrile
  5. concentrationthe combined filtrate was concentrated
  6. customPurification by flash silica gel chromatography

Sources & evidence

ORD record
ord-a24c17fc9c684139a13d39ea5bbf41cc
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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