Cesium carbonate → 2,6-dichloro-N-(2-(3-fluoropyridin-2-ylamino)pyridin-4-yl)benzamide

HRID 449890Notes

Reaction equation

HRID 449890 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[F:19][C:20]1[C:21]([NH2:26])=[N:22][CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:26][C:21]2[C:20]([F:19])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH:7]=1)=[O:18]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27628092-Amino-3-fluoropyridineHCID 75464886N-(2-Bromopyridin-4-yl)-2,6-dichlorobenzamide

Product 1

HCID 596180762,6-dichloro-N-(2-(3-fluoropyridin-2-ylamino)pyridin-4-yl)benzamideYield 344.6%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 25 mL microwave tube containing N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (100 mg, 0.29 mmol), 3-fluoropyridin-2-amine (42 mg, 0.38 mmol), Pd2(dba)3 (8 mg, 0.008 mmol), Cs2CO3 (190 mg, 0.58 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 4 mg, 0.003 mmol), and dioxane (15 mL) was degassed and then charged by N2 (3×). The resulting mixture was then irradiated in a microwave reactor at 130° C. for 30 min. The mixture was diluted with dioxane (20 mL) and filtered through Celite. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80%, 10 min) to afford the desired product (377 mg, yield: 45%). 1H NMR (400 MHz, DMSO) δ 11.07 (s, 1H), 8.98 (s, 1H), 8.28-8.01 (m, 3H), 7.70-7.48 (m, 4H), 7.37 (s, 1H), 7.01 (s, 1H). LCMS (ESI) m/z: 378.5 [M+H+].

Workup

  1. customwas degassed
  2. additioncharged by N2 (3×)
  3. customThe resulting mixture was then irradiated in a microwave reactor at 130° C. for 30 min
  4. additionThe mixture was diluted with dioxane (20 mL)
  5. filtrationfiltered through Celite
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by reverse-phase HPLC (Gemini, 200 mm×25 mm, gradient: CH3CN/0.05% NH3.H2O, 50-80%, 10 min)

Sources & evidence

ORD record
ord-6c7eea4cba0a4ae2932f2d5c5b6c8edb
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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