Water → (R)-4-(4-((2,4-dimethoxybenzyl)amino)-1-(1-tosyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide

HRID 62464Notes

Reaction equation

HRID 62464 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=2[O:21][CH3:22])[N:4]([C@@H:23]2[CH2:31][CH2:30][CH2:29][C:28]3[N:27]([S:32]([C:35]4[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=4)(=[O:34])=[O:33])[N:26]=[CH:25][C:24]2=3)[N:3]=1.CC1(C)C(C)(C)OB([C:50]2[CH:68]=[CH:67][C:53]([C:54]([NH:56][C:57]3[CH:62]=[C:61]([C:63]([F:66])([F:65])[F:64])[CH:60]=[CH:59][N:58]=3)=[O:55])=[CH:52][CH:51]=2)O1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:22][O:21][C:14]1[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:13]=1[CH2:12][NH:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@@H:23]3[CH2:31][CH2:30][CH2:29][C:28]4[N:27]([S:32]([C:35]5[CH:36]=[CH:37][C:38]([CH3:39])=[CH:40][CH:41]=5)(=[O:33])=[O:34])[N:26]=[CH:25][C:24]3=4)[N:3]=[C:2]([C:50]3[CH:68]=[CH:67][C:53]([C:54]([NH:56][C:57]4[CH:62]=[C:61]([C:63]([F:64])([F:65])[F:66])[CH:60]=[CH:59][N:58]=4)=[O:55])=[CH:52][CH:51]=3)[C:10]=12

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 712227974-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamideHCID 90303936(R)-3-bromo-N-(2,4-dimethoxybenzyl)-1-(1-tosyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 90304124(R)-4-(4-((2,4-dimethoxybenzyl)amino)-1-(1-tosyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamideYield 87.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

The mixture of (R)-3-bromo-N-(2,4-dimethoxybenzyl)-1-(1-tosyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (80 mg, 0.125 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (59 mg, 0.150 mmol), Pd(PPh3)2Cl2 (9.2 mg, 0.0125 mmol) and K2CO3 (43 mg, 0.313 mmol) in dioxane/H2O (3 mL/0.3 mL) was stirred for 2 h at 90° C. under nitrogen atmosphere. Then the mixture was added water and extracted with DCM. The combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. Concentrated in vacuo and the residue was purified with silica gel chromatography with PE/EA=1/1 to give (R)-4-(4-((2,4-dimethoxybenzyl)amino)-1-(1-tosyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (90 mg, yield 87.2%) as yellow solid.

Workup

  1. extractionextracted with DCM
  2. washThe combined organic layer was washed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationConcentrated in vacuo
  5. customthe residue was purified with silica gel chromatography with PE/EA=1/1

Sources & evidence

ORD record
ord-3612400dd06b457aa0aa1ba65c855177
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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