Diethyl Ether → HCID 66585034, compound

HRID 2369017Notes

Reaction equation

HRID 2369017 reaction equation
[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:28]=[O:29])[CH:9]=1.[CH2:40]1COCC1.C[Mg]Br.CCOCC>O>[CH3:1][Si:2]([CH3:39])([CH3:38])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:17]3[CH:18]=[N:19][C:20]4[C:25]([CH:26]=3)=[CH:24][C:23]([F:27])=[CH:22][CH:21]=4)=[C:12]2[N:11]=[C:10]([CH:28]([OH:29])[CH3:40])[CH:9]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 86664794HCID 86664794, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 66585034HCID 66585034, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidine-5-carbaldehyde (11.0 g, 19.4 mmol) in anhydrous THF (200 mL, 2 mol) under nitrogen at 0° C. was added 3M methylmagnesium bromide in ether (9.69 mL, 29.0 mmol) dropwise. After 1 hour the reaction was complete by HPLC. Water (10 mL) was added over a 15 minute period to quench the reaction. Removed the flask from the ice bath and concentrated in vacuo. Dissolved the remaining residue in ethyl acetate, washed three times with water and then twice with brine. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Purified the remaining crude material by flash chromatography (5-40% EtOAc/hex) to afford 1-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)ethanol (6.8 g; 60% yield) as a yellow solid. HPLC: 7.54 min (Method C). LCMS: ESI+ m/z of 584 (M+H)

Workup

  1. customto quench
  2. customthe reaction
  3. customRemoved the flask from the ice bath
  4. concentrationconcentrated in vacuo
  5. dissolutionDissolved the remaining residue in ethyl acetate
  6. washwashed three times with water
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurified the remaining crude material by flash chromatography (5-40% EtOAc/hex)

Sources & evidence

ORD record
ord-012896ca31c94f84baa7f645aece7dd2
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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