Benzylamine → [3-(6-benzylamino-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-piperidin-1-yl-ethyl)-amine

HRID 1809712Notes

Reaction equation

HRID 1809712 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][C:13]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[N:14][CH:15]=3)[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:34]([NH2:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:34]([NH:41][C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][C:13]([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[N:14][CH:15]=3)[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:9]=2)[CH:5]=[CH:4][CH:3]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86667964[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-piperidin-1-yl-ethyl)-amine

Product 1

HCID 68109557[3-(6-benzylamino-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-piperidin-1-yl-ethyl)-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A sealed tube was charged with [3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-piperidin-1-yl-ethyl)-amine (from Example 41 supra) (285 mg, 0.54 mmol), benzylamine (69 mg, 0.65 mmol), Pd2(dba)3 (20 mg), DavePhos (30 mg), tBuONa (61 mg, 0.65 mmol) and dioxane (10 mL). This mixture was stirred at 105° C. under an atmosphere of N2 for 16 hours. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was partitioned between water and dichloromethane. The water layer was extracted with dichloromethane twice. The combined organics was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by a column chromatography (silica gel, 8 g, 200-300 mesh, eluting with MeOH:dichloromethane, 1:100 to 1:50 to give [3-(6-benzylamino-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-piperidin-1-yl-ethyl)-amine as a light-yellow oil. (Yield 131 mg, 43.4%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was partitioned between water and dichloromethane
  4. extractionThe water layer was extracted with dichloromethane twice
  5. dry with materialThe combined organics was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by a column chromatography (silica gel, 8 g, 200-300 mesh
  9. washeluting with MeOH

Sources & evidence

ORD record
ord-7cf518499f974d4d8a4dd663d6cf4904
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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