Sodium Carbonate → {2-hydroxy-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone

HRID 1171089Notes

Reaction equation

HRID 1171089 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.Br[C:36]1[CH:37]=[CH:38][C:39]([OH:50])=[C:40]([C:42]([N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)=[O:43])[CH:41]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>C(#N)C.ClCCl>[OH:50][C:39]1[CH:38]=[CH:37][C:36]([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]([CH3:33])([CH3:34])[CH3:32])[C:12]3=[N:13][CH:14]=2)=[CH:41][C:40]=1[C:42]([N:44]1[CH2:45][CH2:46][O:47][CH2:48][CH2:49]1)=[O:43]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 17471603(5-Bromo-2-hydroxy-phenyl)-morpholin-4-yl-methanoneHCID 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 68617729{2-hydroxy-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanoneYield 30%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

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 (100 mg, 0.21 mmol), (5-bromo-2-hydroxy-phenyl)-morpholin-4-yl-methanone (66 mg (0.23 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichlormethane adduct (9 mg, 11 μmol) in acetonitrile (2 mL) and aqueous solution of sodium carbonate (2M, 2 mL) was irradiated in a Personal Chemistry Optimizer at 135° C. for 20 min. The crude reaction mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous phase was then extracted with dichloromethane and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was then purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford {2-hydroxy-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone (35 mg, 30% yield) as a colorless solid. 1H-NMR (500 MHz, d6-DMSO) δ 8.86 (d, 1H), 8.27 (d, 1H), 7.64 (dd, 1H), 7.62 (dd, 1H), 7.54 (d, 1H), 7.49 (ddd, 1H), 7.24 (d, br, 1H), 7.11 (ddd, 1H), 7.00 (d, 1H), 5.84 (s, 2H), 3.84 (s, 3H), 3.69 (t, 2H), 3.7-3.2 (m, 8H), 0.86 (t, 2H), −0.08 (s, 9H). MS: m/z 583 [MNa+], 561 [MH+], 443 [MH+-(Me3Si(CH2)2O)]

Workup

  1. customwas irradiated in a Personal Chemistry Optimizer at 135° C. for 20 min
  2. customThe crude reaction mixture
  3. extractionThe aqueous phase was then extracted with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was then purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-38eedc1c1d4f4a7e87153796cf6d73b1
Source dataset
uspto-grants-2010_11
Patent number
US07829558B2

Reaction notes

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