Potassium Carbonate → HCID 68108456, compound

HRID 1809747Notes

Reaction equation

HRID 1809747 reaction equation
[C:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:40]([O:44][C:45](=[O:57])[NH:46][CH2:47][CH2:48][CH:49]([NH2:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([CH3:43])([CH3:42])[CH3:41].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:1]([O:5][C:6](=[O:39])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:56][CH:49]([C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)[CH2:48][CH2:47][NH:46][C:45]([O:44][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:57])[N:25]=4)[C:18]3=[CH:17][N:16]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 57826906HCID 57826906, compoundHCID 86667966{4-[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

Product 1

HCID 68108456HCID 68108456, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
130 °C

Procedure

A sealed tube was charged with {4-[3-(6-bromo-pyridin-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 33 supra) (618 mg, 1.0 mmol), (3-amino-3-phenyl-propyl)-carbamic acid tert-butyl ester (from Example 2 supra) (300 mg, 1.2 mmol), DavePhos (78 mg, 0.20 mmol), K2CO3 (166 mg, 1.2 mmol), Pd2(dba)3 (44 mg, 0.05 mmol) and 1,4-dioxane (20 mL). The mixture was stirred at 130° C. for 8 hours under an atmosphere of N2. The mixture was cooled and filtered. The filtrate was evaporated under reduced pressure and the residue was purified first by column chromatography (ethyl acetate:petroleum ether, 1:3), then by prep-HPLC to give {4-[3-[6-(3-tert-butoxycarbonylamino-1-phenyl-propylamino)-pyridin-2-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester. (Yield 71 mg, 9.0%).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. customThe filtrate was evaporated under reduced pressure
  4. customthe residue was purified first by column chromatography (ethyl acetate:petroleum ether, 1:3)

Sources & evidence

ORD record
ord-e6f6c762a564451881cd2d43c156399b
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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