4-Chlorobenzylamine → 2-Morpholinoethylamine

HRID 1809721Notes

Reaction equation

HRID 1809721 reaction equation
BrC1C=C(C2C3C(=NC([NH:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=NC=3)N(COCC[Si](C)(C)C)N=2)C=CC=1.ClC1C=CC(CN)=CC=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(O[Na])(C)(C)C>O1CCOCC1.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]>[N:20]1([CH2:19][CH2:18][NH2:17])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 660364-ChlorobenzylamineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68109320[3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 4082852-Morpholinoethylamine

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of [3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo-[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 40 supra) (250 mg, 0.468 mmol), 4-chlorobenzylamine (80 mg, 0.564 mmol), DavePhos (37 mg) and t-BuONa (54 mg, 0.564 mmol) in 1,4-dioxane (10 mL), Pd2(dba)3 (42 mg, 0.073 mmol) was added in one portion under N2 atmosphere. The resultant mixture was stirred at 100° C. for 6 hours. The mixture was cooled and filtered; the filtrate was evaporated under reduced pressure to give the crude product. It was purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH, 100:1, v/v) to give 3-[3-(4-chloro-benzylamino)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-(2-morpholin-4-yl-ethyl)-amine. (Yield 140 mg, 50%).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. customthe filtrate was evaporated under reduced pressure
  4. customto give the crude product
  5. customIt was purified by chromatography (silica gel, 200-300 mesh, dichloromethane

Sources & evidence

ORD record
ord-b1db07047d9c448cb2686b5cf12b686b
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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