Cesium carbonate → HCID 117678220, compound

HRID 1778190Notes

Reaction equation

HRID 1778190 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:11][N:10]([CH:12]3[CH2:15][O:14][CH2:13]3)[CH2:9]2)[CH:5]=[C:4](Cl)[N:3]=1.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.[CH:42]1([B-](F)(F)F)[CH2:44][CH2:43]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].[F:56][CH:57]([F:75])[O:58][C:59]1[C:60]([NH2:74])=[N:61][CH:62]=[C:63](B2OC(C)(C)C(C)(C)O2)[CH:64]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd+2]>[CH:42]1([C:4]2[N:3]=[C:2]([C:63]3[CH:62]=[N:61][C:60]([NH2:74])=[C:59]([O:58][CH:57]([F:56])[F:75])[CH:64]=3)[CH:7]=[C:6]([CH:8]3[CH2:11][N:10]([CH:12]4[CH2:15][O:14][CH2:13]4)[CH2:9]3)[CH:5]=2)[CH2:44][CH2:43]1

Participants

10

Reactant 7

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 498535313-(difluoroMethoxy)-5-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-aMineHCID 117678219HCID 117678219, compound

Product 1

HCID 117678220HCID 117678220, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
110 °C

Procedure

A vial was charged with 2,6-dichloro-4-(1-(oxetan-3-yl)azetidin-3-yl)pyridine (133 mg, 0.513 mmol), palladium(II) acetate (5.8 mg, 5 mol %), butyldi-1-adamantylphosphine (14.5 mg, 7.5 mol %), potassium cyclopropyltrifluoroborate (79.9 mg, 0.523 mmol), and cesium carbonate (502 mg, 1.54 mmol) and purged under nitrogen before the addition of degassed toluene (2.6 mL) and deionized water (0.25 mL). The mixture was stirred at 110° C. overnight and then cooled to rt. To the mixture was added 3-(difluoromethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (220 mg, 0.770 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) (38.7 mg, 0.0513 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (50.0 mg, 0.103 mmol), and potassium phosphate tribasic monohydrate (366 mg, 1.54 mmol). The vial was purged with nitrogen gas, sealed, and stirred at 110° C. for 2 h. After cooling to rt, the mixture was concentrated to dryness. The reaction residue thus obtained was purified by flash column chromatography (100:0-80:20 CH2Cl2/MeOH) and by RPLC to afford the title compound as a white solid (22.9 mg, 12% over 2 steps); 1H NMR (400 MHz, DMSO) δ 8.53 (d, J=1.9 Hz, 1H), 7.94 (s, 1H), 7.50 (d, J=1.9 Hz, 1H), 7.17 (t, J=74.0 Hz, 1H), 7.16 (s, 1H), 6.35 (br s, 2H), 4.62-4.50 (m, 2H), 4.45-4.32 (m, 2H), 3.82-3.70 (m, 1H), 3.70-3.60 (m, 3H), 3.28-3.23 (m, 2H), 2.17-2.03 (m, 1H), 1.05-0.85 (m, 4H).

Workup

  1. custompurged under nitrogen before the addition of degassed toluene (2.6 mL) and deionized water (0.25 mL)
  2. temperaturecooled to rt
  3. customThe vial was purged with nitrogen gas
  4. customsealed
  5. stirringstirred at 110° C. for 2 h
  6. temperatureAfter cooling to rt
  7. concentrationthe mixture was concentrated to dryness
  8. customThe reaction residue thus obtained
  9. customwas purified by flash column chromatography (100:0-80:20 CH2Cl2/MeOH) and by RPLC

Sources & evidence

ORD record
ord-b95e24da34f443cbac853827e7beef24
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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