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

HRID 522891Notes

Reaction equation

HRID 522891 reaction equation
Br[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.[NH2:20][C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=1)[C:24]([NH:26][CH3:27])=[O:25].C(=O)([O-])[O-].[K+].[K+].CC(O)(C)C>CCOC(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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[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:20][C:21]4[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=4)[C:24]([NH:26][CH3:27])=[O:25])[CH:7]=[CH:6][CH:5]=3)[CH2:9]2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 6765263-Amino-N-methylbenzamideHCID 86685247HCID 86685247, compound

Product 1

HCID 673555953-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamideYield 93%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a disposable sealed tube was charged 2-bromo-6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridine (100.0 mg, 0.309 mmol), 3-amino-N-methylbenzamide (69.7 mg, 0.464 mmol), potassium carbonate (59.9 mg, 0.433 mmol) followed by X-Phos (2.95 mg, 6.19 μmol) and Pd2(dba)3 (1.417 mg, 1.547 μmol). The tube was fitted with a septum with an argon inlet for 5-10 min, when t-BuOH (1.0 mL) was added. The reaction mixture was then heated to 100° C. for 7 h, cooled to RT, diluted with EtOAc, and filtered through Celite® (diatomaceous earth) with EtOAc. The filtrate was concentrated and purified using MPLC (5 g cartridge, 12 g column, 0 to 75% EtOAc-hexanes) giving 3-(6-(3-(4-fluorophenoxy)azetidin-1-yl)pyridin-2-ylamino)-N-methylbenzamide (112.8 mg).

Workup

  1. customThe tube was fitted with a septum with an argon inlet for 5-10 min
  2. temperaturecooled to RT
  3. filtrationfiltered through Celite® (diatomaceous earth) with EtOAc
  4. concentrationThe filtrate was concentrated
  5. custompurified

Sources & evidence

ORD record
ord-365b3035c4ba4780bca8ca317caea587
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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