Potassium Carbonate → HCID 68108314, compound

HRID 1809757Notes

Reaction equation

HRID 1809757 reaction equation
[C:1]([O:5][C:6](=[O:50])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([C:31]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[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:51]([O:55][C:56](=[O:67])[NH:57][CH2:58][CH:59]([NH2:66])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)([CH3:54])([CH3:53])[CH3:52].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:50])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[N:20]=[C:19]3[N:21]([C:31]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:22]=[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([NH:66][CH:59]([C:60]5[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=5)[CH2:58][NH:57][C:56]([O:55][C:51]([CH3:54])([CH3:52])[CH3:53])=[O:67])[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 2771847tert-butyl N-(2-amino-2-phenylethyl)carbamateHCID 86667967{-4-[3-(6-bromo-pyridin-2-yl)-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

Product 1

HCID 68108314HCID 68108314, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
132 °C

Procedure

A sealed tube was charged with {4-[3-(6-bromo-pyridin-2-yl)-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (from Example 35 supra) (860 mg, 1.18 mmol), (2-amino-2-phenyl-ethyl)-carbamic acid tert-butyl ester (from Example 1 supra) (390 mg, 1.65 mmol), Pd2(dba)3 (68 mg, 0.12 mmol), DavePhos (93 mg, 0.24 mmol), K2CO3 (228 mg, 1.65 mmol) and dioxane (30 mL), this mixture was stirred at 132° C. under an atmosphere of N2 for 7 hours. After cooling to room temperature, the mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 26 g, 100-200 mesh, eluting with petroleum ether:ethyl acetate, 1:1) to give crude product which was further purified by prep-HPLC to afford (4-{3-[6-(2-tert-Butoxycarbonylamino-1-phenyl-ethylamino)-pyridin-2-yl]-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino}-cyclohexyl)-carbamic acid tert-butyl ester. (Yield 103 mg, 9.86%).

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, 26 g, 100-200 mesh, eluting with petroleum ether:ethyl acetate, 1:1)
  5. customto give crude product which
  6. customwas further purified by prep-HPLC

Sources & evidence

ORD record
ord-0536229b3f5242b5a5106d16389b8b78
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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