Potassium Carbonate → HCID 68108371, compound

HRID 1809759Notes

Reaction equation

HRID 1809759 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][O: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:34]([O:38][C:39](=[O:51])[NH:40][CH2:41][CH2:42][CH:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([CH3:37])([CH3:36])[CH3:35].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>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>[C:34]([O:38][C:39](=[O:51])[NH:40][CH2:41][CH2:42][CH:43]([NH:50][C:2]1[CH:3]=[CH:4][CH:5]=[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][O: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)[N:7]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57826906Tert-butyl 3-amino-3-phenylpropylcarbamateHCID 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

Product 1

HCID 68108371HCID 68108371, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
132 °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-morpholin-4-yl-ethyl)-amine (from Example 32 supra) (500 mg, 0.936 mmol), (3-amino-3-phenyl-propyl)-carbamic acid tert-butyl ester (from Example 2 supra) (328 mg, 1.31 mmol), Pd2(dba)3 (54 mg, 0.094 mmol), DavePhos (74 mg, 0.187 mmol), K2CO3 (181 mg, 1.31 mmol) and dioxane (20 mL). The mixture was stirred at 132° C. under an atmosphere of N2 for 7.5 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 14 g, 100-200 mesh, eluting with dichloromethane:MeOH, 80:1) to give crude product which was further purified by prep-HPLC to afford (3-{6-[6-(2-morpholin-4-yl-ethylamino)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-pyridin-2-ylamino}-3-phenyl-propyl)-carbamic acid tert-butyl ester. (Yield 147 mg, 16%).

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (silica gel, 14 g, 100-200 mesh, eluting with dichloromethane:MeOH, 80:1)
  5. customto give crude product which
  6. customwas further purified by prep-HPLC

Sources & evidence

ORD record
ord-cb1e67d2949b4349a56b51457f156551
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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