Water → [3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine

HRID 1809700Notes

Reaction equation

HRID 1809700 reaction equation
[CH3:1][Si:2]([CH2:5][CH2:6][O:7][CH2:8]Cl)([CH3:4])[CH3:3].[Br:10][C:11]1[N:16]=[C:15]([C:17]2[C:25]3[C:20](=[N:21][C:22](Cl)=[N:23][CH:24]=3)[NH:19][N:18]=2)[CH:14]=[CH:13][CH:12]=1.[O:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][NH2:35])[CH2:29][CH2:28]1.O>CN(C=O)C>[Br:10][C:11]1[N:16]=[C:15]([C:17]2[C:25]3[C:20](=[N:21][C:22]([NH:35][CH2:34][CH2:33][N:30]4[CH2:31][CH2:32][O:27][CH2:28][CH2:29]4)=[N:23][CH:24]=3)[N:19]([CH2:8][O:7][CH2:6][CH2:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[N:18]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 4082852-MorpholinoethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178478327HCID 178478327, compound

Product 1

HCID 86667960[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

SEM-Cl (5.15 g, 30.9 mmol) was added dropwise to a solution of 3-(6-bromo-pyridin-2-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidine (from Example 30 supra) (8.0 g, 25.8 mmol) and TEA (10.4 g, 103 mmol) in DMF (170 mL). The reaction was stirred at room temperature for 40 minutes. Then 2-morpholinoethanamine (4.03 g, 30.9 mmol) was added dropwise to the above solution. The mixture was heated at 55° C. for 12 hours. After cooling to room temperature, the reaction mixture was poured into water (500 mL) and extracted with ethyl acetate. Ethyl acetate solution was evaporated and purified by chromatography (silica gel, dichloromethane:MeOH, 50:1) to afford [3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine as yellow solid. (Yield 5.6 g, 41%).

Workup

  1. temperatureThe mixture was heated at 55° C. for 12 hours
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with ethyl acetate
  4. customEthyl acetate solution was evaporated
  5. custompurified by chromatography (silica gel, dichloromethane:MeOH, 50:1)

Sources & evidence

ORD record
ord-1a52afef5212412d84e862be1522234b
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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