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 2389007Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2389007
[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]

Komponenten

6

Edukt 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

Produkt 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-benzamideAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

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)-ferrocenepalladium(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, J1=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, J1=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+]

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-836bee3acdf04b03b78dd34a2a234e02
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08268994B2

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