Cesium carbonate → 3-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamide

HRID 522922Notes

Reaction equation

HRID 522922 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:9]2)[N:3]=1.N[C:21]1[CH:30]=[CH:29][C:24]([C:25]([NH:27][CH3:28])=[O:26])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([N:86](C)C)=O>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]>[F:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH:10]2[CH2:11][N:8]([C:4]3[N:3]=[C:2]([NH:86][C:22]4[CH:23]=[C:24]([CH:29]=[CH:30][CH:21]=4)[C:25]([NH:27][CH3:28])=[O:26])[CH:7]=[CH:6][CH:5]=3)[CH2:9]2)=[CH:14][CH:15]=1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 2355164-Amino-N-methylbenzamideHCID 634876Binap, (A+-)-HCID 866852582-Chloro-6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridine

Product 1

HCID 673555953-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamideYield 13%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

To a solution of 2-chloro-6-(3-(4-fluorophenoxy) azetidin-1-yl)pyridine (500 mg, 1.79 mmoL) and 4-amino-N-methylbenzamide (270 mg, 1.79 mmol) in dimethylacetamide (5 mL, 3 mL/mmol) was added cesium carbonate (873 mg, 2.68 mmol) and the reaction was degassed for 15 min. Pd2(dba)3 (81 mg, 0.089 mmol) and BINAP (55 mg, 0.089 mmol) were added and the reaction was allowed to heat at 120° C. in the microwave. The reaction was quenched with water and extracted with EtOAc (2×50 mL). The organic extracts were washed with brine, dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to afford 3-(6-(3-(4-fluorophenoxy) azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamide (61 mg, 13%) as a solid. Observed mass (M+1): 393.1. The following compounds were prepared as described in Example V above using appropriate starting materials.

Workup

  1. customthe reaction was degassed for 15 min
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (2×50 mL)
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-eee1e11f6b46466aa9bba959a9aea0bb
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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