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

HRID 869955Notes

Reaction equation

HRID 869955 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[C:34](B(O)O)=[CH:33][C:32]([CH3:38])=[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:34]5[C:29]([O:28][CH3:27])=[N:30][CH:31]=[C:32]([CH3:38])[CH:33]=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 27631282-Methoxy-5-methylpyridine-3-boronic acidHCID 89228784HCID 89228784, compound

Product 1

HCID 687393981-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4,5'-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideYield 57%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (114 mg, 0.3 mmol) and 2-methoxy-5-methylpyridin-3-ylboronic acid (75 mg, 0.45 mmol) in DME (3 mL) and Na2CO3 (2M, 0.3 mL, 0.6 mmol) was added Pd(PPh3)4 (17 mg, 0.015 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The reaction was re-partitioned between EtOAc and H2O and the aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (0-20% EtOAc-Hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,4,5′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (80 mg, 57%). 1H NMR (400 MHz, CDCl3) 8.02 (s, 1H), 7.99 (d, J=1.6 Hz, 1H), 7.59 (s, 1H), 7.31 (d, J=2.1 Hz, 1H), 7.20-7.16 (m, 2H), 7.04 (d, J=8.1 Hz, 1H), 3.85 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 1.95 (s, 3H), 1.73 (dd, J=3.8, 6.9 Hz, 2H), 1.14 (dd, J=3.9, 7.0 Hz, 2H). Retention time: 2.02 min; ESI-MS m/z calc. 467.5. found 468.2 (M+H)+.

Workup

  1. customThe reaction was re-partitioned between EtOAc and H2O
  2. extractionthe aqueous layer was extracted with EtOAc twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (0-20% EtOAc-Hexane)

Sources & evidence

ORD record
ord-32e7fa32d75b4b059d7dadec71fa22a6
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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