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Potassium Carbonate → 2-methoxy-5-((2-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

HRID 1471696
Notes
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Reaction equation

HRID 1471696 reaction equation
Br[C:2]1[C:7]([CH2:8][O:9][C:10]2[C:15]([CH:16]=[O:17])=[CH:14][C:13]([O:18][CH3:19])=[N:12][CH:11]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:20][C:21]1[CH:22]=[N:23][N:24]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[C:25]=1B(O)O.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>[CH3:19][O:18][C:13]1[CH:14]=[C:15]([C:10]([O:9][CH2:8][C:7]2[C:2]([C:25]3[N:24]([CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][O:30]4)[N:23]=[CH:22][C:21]=3[CH3:20])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:11][N:12]=1)[CH:16]=[O:17]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 68490911[4-methyl-1-(oxan-2-yl)-1H-pyrazol-5-yl]boronic acidHCID 716217595-((2-Bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde

Product 1

HCID 866907482-methoxy-5-((2-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehydeYield 87%

Reagents, catalysts & solvents 2

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

To a mixture of 5-((2-bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde (100 mg, 0.31 mmol, 1 equiv), 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-ylboronic acid (98 mg, 0.47 mmol, 1.5 equiv), Pd(PPh3)4 (70 mg, 0.06 mmol, 0.2 equiv), K2CO3 (171 mg, 1.24 mmol, 4 equiv) in a 5 mL microwave tube was 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-((2-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (110 mg, 87%) as a colorless oil. LRMS (M+H+) m/z 409.2.

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-a24c653b5f6948dfb8f097cd0fbeea7a
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09012450B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes