Diisopropylethylamine → 6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine 6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-pyrazolo[3,4-b]pyridine

HRID 2209303Notes

Reaction equation

HRID 2209303 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][N:9]=[CH:10][C:5]2=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:20][Si:21]([CH3:28])([CH3:27])[CH2:22][CH2:23][O:24][CH2:25]Cl>C(Cl)Cl.CCOC(C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:28])([CH3:27])[CH3:20])[N:9]=[CH:10][C:5]2=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[N:8][N:9]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:28])([CH3:27])[CH3:20])[CH:10]=2)[N:7]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 454802836-Chloro-1h-pyrazolo[3,4-b]pyridine

Product 1

HCID 1317359876-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine 6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-pyrazolo[3,4-b]pyridineYield 65.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-chloro-1H-pyrazolo[3,4-b]pyridine (500 mg, 3.3 mmol) was suspended in DCM (10 mL) and N,N-diisopropylethylamine (1.7 mL, 9.8 mmol) was added followed by 2-(trimethylsilyl)ethoxymethyl chloride (1.2 mL, 6.78 mmol). After stifling 3.5 h, the reaction mixture was diluted with EtOAc and water. The organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography (5-50% EtOAc in hexanes) to provide 610 mg of the first-eluting isomer 6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine (or 6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-pyrazolo[3,4-b]pyridine, regiochemistry not determined) 7.54. Uncertainty in this assignment is implicit in other depictions of Intermediate 7.54. LCMS-ESI+ (m/z): [M+H]+ calcd for C12H19ClN3OSi: 284.10; found: 283.79.

Workup

  1. dry with materialThe organic phase was dried over Na2SO4
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto afford a crude residue that
  5. customwas purified by silica gel chromatography (5-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9ccaa660e1cb46f7a5bfca0b91336d4c
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…