Sodium Carbonate → 1-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6'-methoxy-2',3,4-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869943Notes

Reaction equation

HRID 869943 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[C:4]([CH3:25])[C:3]=1[CH3:26].[CH3:27][O:28][C:29]1[N:34]=[C:33]([CH3:35])[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:32]5[C:33]([CH3:35])=[N:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=5)[C:3]([CH3:26])=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 674874826-Methoxy-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 89228784HCID 89228784, compound

Product 1

HCID 710530381-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6'-methoxy-2',3,4-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 53.5%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (70 mg, 0.18 mmol), 6-methoxy-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (69 mg, 0.27 mmol) and tetrakis(triphenylphosphine)-palladium (0) (21 mg, 0.018 mmol) in 1,2-dimethoxyethane (2.0 mL), 2 M Na2CO3 (276 μL, 0.55 mmol) was added. The reaction mixture was stirred and heated at 80° C. for 20 hours under N2 atmosphere. The reaction mixture was diluted with ethyl acetate (5 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-30% ethyl acetate in hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-2′,3,4-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (45 mg, 52%). ESI-MS m/z calc. 467.5. found 468.3 (M+1)+. Retention time 1.80 minutes.

Workup

  1. dry with materialdried over Na2SO4
  2. filtrationfiltered
  3. customevaporated under reduced pressure
  4. customThe crude product was purified by column chromatography on silica gel (0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e9571594a02d46f784c943e065c09474
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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