Sodium Carbonate → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4-dimethyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 870017Notes

Reaction equation

HRID 870017 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[CH:34]=[C:33](B(O)O)[CH:32]=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>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:33]5[CH:32]=[CH:31][N:30]=[C:29]([O:28][CH3:27])[CH:34]=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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 23546919(2-Methoxypyridin-4-yl)boronic acidHCID 89228784HCID 89228784, compound

Product 1

HCID 687394061-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4-dimethyl-2,4'-bipyridin-6-yl)cyclopropanecarboxamideYield 88.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (38 mg, 0.1 mmol) in DME (1 mL) was added to a reaction tube containing 2-methoxypyridin-4-ylboronic acid (46 mg, 0.15 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol). Saturated Na2CO3 solution was added (100 μL) and the reaction was stirred at 80° C. overnight. The reaction was filtered, concentrated and purified by column chromatography (0-50% ethyl acetate in hexanes) to obtain 40 mg (44%) of a clear oil. ESI-MS m/z calc. 453.4. found 454.3 (M+1)+. Retention times: 2.06 minutes. H NMR (400 MHz, DMSO) 8.85 (s, 1H), 8.20 (d, J=5.2 Hz, 1H), 7.86 (s, 1H), 7.54 (d, J=1.5 Hz, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.32 (dd, J=1.6, 8.3 Hz, 1H), 6.97 (dd, J=1.2, 5.2 Hz, 1H), 6.77 (s, 1H), 3.87 (s, 3H), 2.31 (s, 3H), 2.09 (s, 3H), 1.51-1.48 (m, 2H), 1.17-1.15 (m, 2H).

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated
  3. custompurified by column chromatography (0-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-51f190f50bd847d484d8233058127d23
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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