Potassium Carbonate → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(6'-methoxy-3-methyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869913Notes

Reaction equation

HRID 869913 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]=[CH:4][C:3]=1[CH3:25].[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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:32]=[N:33][C:28]([O:27][CH3:26])=[CH:29][CH:30]=5)[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide

Product 1

HCID 687389231-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(6'-methoxy-3-methyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

N-(6-Chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (660 mg, 1.80 mmol) was dissolved in 18 mL of 1,2-dimethoxyethane (DME) in a microwave reactor tube. 6-Methoxypyridin-3-ylboronic acid (358 mg, 2.34 mmol), 2.4 mL of an aqueous 2 M potassium carbonate solution, and tetrakis(triphenylphospine)palladium(0) (Pd(PPh3)4, 102 mg, 0.0882 mmol) were added and the reaction mixture was heated at 120° C. in a microwave reactor for 20 minutes. The resulting material was cooled to room temperature, filtered, and the layers were separated. The crude product was evaporated to dryness and then purified on 40 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (482 mg, 61%). ESI-MS m/z calc. 439.1. found 440.1 (M+1)+ Retention time 1.95 minutes.

Workup

  1. temperatureThe resulting material was cooled to room temperature
  2. filtrationfiltered
  3. customthe layers were separated
  4. customThe crude product was evaporated to dryness
  5. custompurified on 40 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-611acf297eb747089aa9d9aeef2e6d8e
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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