Water → 3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4-methyl-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1982944

Reaction equation

HRID 1982944 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][O:8][CH2:9][C:10]1[C:18]2[N:17]=[C:16]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25](B5OC(C)(C)C(C)(C)O5)[CH:26]=4)[N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[N:20]=3)[N:15]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[C:14]=2[CH:13]=[CH:12][CH:11]=1.Br[C:54]1[CH:55]=[N:56][CH:57]=[CH:58][C:59]=1[CH3:60].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][O:8][CH2:9][C:10]1[C:18]2[N:17]=[C:16]([C:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([C:54]5[CH:55]=[N:56][CH:57]=[CH:58][C:59]=5[CH3:60])[CH:26]=4)[N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:42])[CH3:43])[N:20]=3)[N:15]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:51])([CH3:52])[CH3:50])[C:14]=2[CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 8176303-Bromo-4-methylpyridineHCID 575811133-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 688869563-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4-methyl-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

An aqueous 2M sodium carbonate solution (0.11 mL, 0.23 mmol) was added to a solution of 3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine Compound 12c (60 mg, 0.09 mmol), 3-bromo-4-methyl-pyridine Compound 13a (10 μl, 0.09 mmol) and tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.01 mmol) in dioxane (1 mL) in a reaction tube. The reaction tube was sealed and heated to 90° C. overnight. After cooling to room temperature, the crude mixture was poured into water (30 mL) and was extract with DCM (2×25 mL). The combined organic layer was dried over sodium sulfate and concentrated. Silica gel chromatography (10% to 50% ethyl acetate/hexanes) gave 3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4-methyl-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine Compound 13b (54 mg, 95%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 9.17 (d, 1H, J=1.5 Hz), 8.92 (d, 1H, J=1.5 Hz), 8.71 (m, 2H), 7.87 (m, 2H), 7.61 (m, 2H), 6.50 (s, 2H), 6.23 (s, 2H), 5.17 (s, 2H), 4.04 (t, 2H, J=6 Hz), 3.86 (t, 2H, J=6 Hz), 3.66 (s, 3H), 2.62 (s, 3H), 1.18 (t, 2H, J=6 Hz); 1.05 (t, 2H, J=6 Hz), 0.18 (s, 9H), 0.05 (s, 9H); MS (ESI) m/z: 631 (M+H+).

Workup

  1. customThe reaction tube was sealed
  2. temperatureAfter cooling to room temperature
  3. extractionwas extract with DCM (2×25 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d835a2dc82274400989c4f64a0fbef96
Source dataset
uspto-grants-2009_06
Patent number
US07541367B2

Linked notes

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