6-Methoxy-5-methylpyridine-3-boronic acid pinacol ester → 1-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6'-methoxy-4,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869941Notes

Reaction equation

HRID 869941 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])[CH:3]=1.[CH3:26][O:27][C:28]1[C:33]([CH3:34])=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][N:29]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].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>[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:31]5[CH:30]=[N:29][C:28]([O:27][CH3:26])=[C:33]([CH3:34])[CH:32]=5)[CH:3]=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

Participants

6

Reactant 2

HCID 574164936-Methoxy-5-methylpyridine-3-boronic acid pinacol esterHCID 87555366HCID 87555366, compound

Product 1

HCID 710530861-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6'-methoxy-4,5'-dimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 40.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent2×HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To N-(6-chloro-4-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (0.15 g, 0.41 mmol), 2-methoxy-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.15 g, 0.61 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.024 g, 0.02 mmol) in 1,2-dimethoxyethane (2.46 mL), aqueous saturated Na2CO3 (410 uL) was added. The reaction mixture was stirred and heated at 80° C. for 18 hours under N2 atmosphere. The reaction mixture was diluted with 1,2-dimethoxyethane, 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-4,5′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (0.075 g, 40%). ESI-MS m/z calc. 453.44. found 454.5 (M+1)+. Retention time 2.24 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-1cc25293ec5946b49427c933c1d40e5b
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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