Acetic Acid → 5-(tetrahydro-2H-thiopyran-4-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 2047167Notes

Reaction equation

HRID 2047167 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][NH:4][N:3]=1.O=[C:8]([CH:12]1[CH2:17][CH2:16][S:15][CH2:14][CH2:13]1)[CH2:9][C:10]#[N:11].[CH3:18][Si:19]([CH2:22][CH2:23][O:24][CH2:25]Cl)([CH3:21])[CH3:20].CCN([CH:33]([CH3:35])C)C(C)C.[C:36]([OH:39])(=O)C>C(Cl)Cl>[S:15]1[CH2:16][CH2:17][CH:12]([C:8]2[CH:9]=[C:10]([N:11]([CH2:36][O:39][CH2:33][CH2:35][Si:19]([CH3:21])([CH3:20])[CH3:18])[CH2:25][O:24][CH2:23][CH2:22][Si:19]([CH3:21])([CH3:20])[CH3:18])[N:3]3[N:4]=[CH:5][CH:6]=[C:2]3[N:1]=2)[CH2:13][CH2:14]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 66584535HCID 66584535, compoundHCID 178418806HCID 178418806, compound

Product 1

HCID 665844755-(tetrahydro-2H-thiopyran-4-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amineYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-aminopyrazole (19.3 mmol, 1.61 g) and compound 3-oxo-3-(tetrahydro-2H-thiopyran-4-yl)propanenitrile (21.3 mmol, 3.60 g) in acetic acid (40 mL) was heated at 100° C. in a sealed tube overnight. After cooling to rt, all the volatiles were removed under reduced pressure to afford a light brownish oil. This brownish oil was dissolve in DCM (60 mL), and then SEMCl (67.6 mmol, 11.9 mL) and DIPEA (135 mmol, 23.5 mL) were added. The resulting reaction mixture was stirred at 45° C. for 1 h. After cooling to rt, all the volatiles were removed under reduced pressure. The residue was diluted with EtOAc (300 mL), filtered and washed with EtOAc. The filtrate was concentrated and the crude product was purified by a SiO2 column (0-30%) to afford compound, 5-(tetrahydro-2H-thiopyran-4-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine as a light brownish oil (9.23 g, 97%). HPLC-MS TR=3.09 min (UV 254 nm, 5 min method); mass calculated for formula C23H42N4O2SSi2 494.3, observed LCMS m/z 495.1 (M+H).

Workup

  1. temperatureAfter cooling to rt
  2. customall the volatiles were removed under reduced pressure
  3. customto afford a light brownish oil
  4. customThe resulting reaction mixture
  5. temperatureAfter cooling to rt
  6. customall the volatiles were removed under reduced pressure
  7. additionThe residue was diluted with EtOAc (300 mL)
  8. filtrationfiltered
  9. washwashed with EtOAc
  10. concentrationThe filtrate was concentrated
  11. customthe crude product was purified by a SiO2 column (0-30%)

Sources & evidence

ORD record
ord-02dc8d96999147cc8ae769663f087439
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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