Potassium Carbonate → N-(4-(1-(2-(dimethylamino)ethylamino)isoquinolin-5-yl)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2356355Notes

Reaction equation

HRID 2356355 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[NH:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16].[OH:18][C:19]([CH3:53])([CH3:52])[CH2:20][N:21]1[C:25]([CH3:26])=[C:24]([C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[O:28])[C:23](=[O:45])[N:22]1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.O1CCOCC1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.O.[Pd]>[CH3:16][N:15]([CH3:17])[CH2:14][CH2:13][NH:12][C:7]1[C:8]2[C:3](=[C:2]([C:33]3[CH:32]=[CH:31][C:30]([NH:29][C:27]([C:24]4[C:23](=[O:45])[N:22]([C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=5)[N:21]([CH2:20][C:19]([OH:18])([CH3:52])[CH3:53])[C:25]=4[CH3:26])=[O:28])=[CH:35][CH:34]=3)[CH:11]=[CH:10][CH:9]=2)[CH:4]=[CH:5][N:6]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593839345-Bromo-N-(2-(dimethylamino)ethyl)isoquinolin-1-amineHCID 593839381-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 24999276N-(4-(1-(2-(dimethylamino)ethylamino)isoquinolin-5-yl)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 73.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

5-Bromo-N-(2-(dimethylamino)ethyl)isoquinolin-1-amine (0.068 g, 0.2 mmol) was added to a microwave vial equipped with a stirbar, along with 1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2,3-dihydro-1H-pyrazole-4-carboxamide (0.2 g, 0.3 mmol). Then 1,4-Dioxane (3 ml, 35 mmol) was added into the mixture, followed by 2M K2CO3 (0.5 ml). Then Fibrecat (2.93% Pd, 0.010 g) was added to the mixture. The vial was capped, then placed into CEM Microwave for 10 minutes at 120° C. with 80 Watts of power supplied through Powermax feature. The mixture was diluted with DCM and water, then collected the organic layer by extracting with DCM (3×10 ml). Combined organics, dried over Na2SO4, filtered and concentrated in-vacuo. The crude was purified by ISCO Amino-propyl chromatography using MeOH/DCM as the eluent. This gave the title compounds as a tan amorphous solid (85 mg). MS (ESI pos. ion) m/z: 579 (MH+). Calc'd exact mass for C34H38N6O3: 578.

Workup

  1. customThe vial was capped
  2. customcollected the organic layer
  3. extractionby extracting with DCM (3×10 ml)
  4. dry with materialCombined organics, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in-vacuo
  7. customThe crude was purified by ISCO Amino-propyl chromatography

Sources & evidence

ORD record
ord-f3095c49e3a64405b3e1140d551411c8
Source dataset
uspto-grants-2010_07
Patent number
US07759344B2

Reaction notes

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