Potassium Carbonate → 2-methoxy-5-((3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)isoquinolin-4-yl)methoxy)isonicotinaldehyde

HRID 1471701Notes

Reaction equation

HRID 1471701 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([C:11]=1[CH2:12][O:13][C:14]1[C:19]([CH:20]=[O:21])=[CH:18][C:17]([O:22][CH3:23])=[N:16][CH:15]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH3:24][Si:25]([CH3:39])([CH3:38])[CH2:26][CH2:27][O:28][CH2:29][N:30]1[C:34](B(O)O)=[CH:33][CH:32]=[N:31]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[CH3:23][O:22][C:17]1[CH:18]=[C:19]([C:14]([O:13][CH2:12][C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[N:3][C:2]=2[C:34]2[N:30]([CH2:29][O:28][CH2:27][CH2:26][Si:25]([CH3:39])([CH3:38])[CH3:24])[N:31]=[CH:32][CH:33]=2)=[CH:15][N:16]=1)[CH:20]=[O:21]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 21874652(1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)boronic acidHCID 866907505-((3-Chloroisoquinolin-4-yl)methoxy)-2-methoxyisonicotinaldehyde

Product 1

HCID 866907522-methoxy-5-((3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)isoquinolin-4-yl)methoxy)isonicotinaldehydeYield 40.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

To a mixture of 5-((3-chloroisoquinolin-4-yl)methoxy)-2-methoxyisonicotinaldehyde (18 mg, 0.05 mmol, 1 equiv), 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-ylboronic acid (20 mg, 0.08 mmol, 1.5 equiv), Pd(PPh3)4 (12 mg, 0.01 mmol, 0.2 equiv), K2CO3 (30 mg, 0.22 mmol, 4 equiv) in a 5 mL microwave tube were added DMF (2 mL). The mixture was heated 30 min at 125° C. in a microwave reactor. The solid was filtered off and the filtrate was concentrated to dryness. The crude was purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-methoxy-5-((3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)isoquinolin-4-yl)methoxy)isonicotinaldehyde (10 mg, 38%) as a white solid. LRMS (M+H+) m/z 491.1.

Workup

  1. filtrationThe solid was filtered off
  2. concentrationthe filtrate was concentrated to dryness
  3. customThe crude was purified on silica gel using
  4. additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record
ord-8bc0ab7856a7436a9e420185c3792bd8
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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