Sodium Hydroxide → HCID 178491796, compound

HRID 2388929Notes

Reaction equation

HRID 2388929 reaction equation
[CH3:1][N:2]([CH3:45])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=5[O:35][CH3:36])=[N:26][N:25](COCC[Si](C)(C)C)[C:22]4=[N:23][CH:24]=3)[CH:14]=2)=[O:12])[CH2:7][CH2:6]1.[OH-].[Na+]>Cl(O)(=O)(=O)=O.CO>[CH3:1][N:2]([CH3:45])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=5[O:35][CH3:36])=[N:26][NH:25][C:22]4=[N:23][CH:24]=3)[CH:14]=2)=[O:12])[CH2:7][CH2:6]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59836165(4-(2-(dimethylamino)ethyl)piperazin-1-yl)(3-(3-(5-fluoro-2-methoxyphenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)methanone

Product 1

HCID 178491796HCID 178491796, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 24247Perchloric AcidSolvent

Procedure

A solution of (4-(2-(dimethylamino)ethyl)piperazin-1-yl)(3-(3-(5-fluoro-2-methoxyphenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)methanone from Step 5 in 5% of perchloric acid in methanol (1 mL) was stirred for 45 minutes at room temperature. Sodium hydroxide solution (2M) was then added to the solution slowly until pH ˜8. Ethyl acetate was then used for extraction and the organic layers were combined and concentrated to dryness, which was then redissolved in methanol (1 mL) and sodium carbonate (2M, 1 mL). The mixture was stirred at room temperature for 15 hours before being diluted with water and extracted with ethyl acetate (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to dryness. Mass triggered reverse phase HPLC purification afforded (4-(2-(dimethylamino)ethyl)piperazin 1-yl)(3-(3-(5-fluoro-2-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)methanone (25.6 mg, 64% yield from 12) as white solids. 1H NMR (500 MHz, CD3OD) δ 2.42 (s, 6H), 2.49 (br, 2H), 2.59 (m, 4H), 2.69 (m, 2H), 3.54 (br, 2H), 3.81 (br, 2H), 3.85 (s, 3H), 7.17 (m, 2H), 7.40 (dd, J=3.0, 9.5 Hz, 1H), 7.44 (d, br, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.72 (br, 1H), 7.77 (d, J=8.5 Hz, 1H), 8.39 (d, J=1.5 Hz, 1H), 8.80 (d, J=2.5 Hz, 1H). MS: m/z 503.2 (M+H+).

Workup

  1. extractionEthyl acetate was then used for extraction
  2. concentrationconcentrated to dryness, which
  3. dissolutionwas then redissolved in methanol (1 mL)
  4. additionbefore being diluted with water
  5. extractionextracted with ethyl acetate (3×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customphase HPLC purification

Sources & evidence

ORD record
ord-7a41d380aaf3485d878017327c97393b
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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