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Dimethylformamide → 3-((4-Formyl-6-methoxypyridin-3-yloxy)methyl)picolinonitrile

HRID 1471694
Notes
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Reaction equation

HRID 1471694 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][N:21](C=O)C>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>[CH:16]([C:15]1[CH:14]=[C:13]([O:18][CH3:19])[N:12]=[CH:11][C:10]=1[O:9][CH2:8][C:7]1[C:2]([C:20]#[N:21])=[N:3][CH:4]=[CH:5][CH:6]=1)=[O:17]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 716217595-((2-Bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde

Product 1

HCID 716217603-((4-Formyl-6-methoxypyridin-3-yloxy)methyl)picolinonitrileYield 84%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
125 °C

Procedure

To a mixture of 5-((2-bromopyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde (100 mg, 0.31 mmol, 1 equiv), Zn (CN)2 (71 mg, 0.62 mmol, 2.0 equiv), Pd(PPh3)4 (72 mg, 0.06 mmol, 0.2 equiv) in a 5 mL microwave tube was added DMF (2 mL). The mixture was heated 15 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 3-((4-formyl-6-methoxypyridin-3-yloxy)methyl)picolinonitrile (71 mg, 84%) as a white solid. 1H NMR (400 MHz; CDCl3) δ=10.54 (s, 1H), 8.86 (d, 1H), 8.22 (s, 1H), 8.20 (d, 1H), 7.74 (dd, 1H), 6.37 (s, 1H) 5.52 (s, 2H), 4.04 (s, 3H). LRMS (M+H+) m/z 270.1.

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-3bbeaeeeb7e44a2e81676ed8a2c1797b
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