Tetrahydrofuran → HCID 67231943, compound

HRID 1260476Notes

Reaction equation

HRID 1260476 reaction equation
Br[C:2]1[C:7]([NH2:8])=[C:6]([Cl:9])[CH:5]=[CH:4][N:3]=1.[CH:10]1(B(O)O)[CH2:12][CH2:11]1.C([O-])([O-])=O.[Cs+].[Cs+].C1COCC1>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[Cl:9][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH:10]2[CH2:12][CH2:11]2)[C:7]=1[NH2:8]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 224762862-Bromo-4-chloropyridin-3-amine

Product 1

HCID 67231943HCID 67231943, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Following a modified synthetic procedure reported in J. Org. Chem. 2003, 68, 5534 a mixture of 2-bromo-4-chloropyridin-3-amine (prepared as described in US2002/0119982) (1.0 eq.), cyclopropylboronic acid (2.0 eq.), Cs2CO3 (3.0 eq.) and PdCl2(dppf)-CH2Cl2 adduct (0.1 eq.) in 10:1 solution THF:H2O (0.14 M) was put in a 10-mL glass vial equipped with a small magnetic stirring bar. The reaction vessel was fitted with a rubber septum, was evacuated and back-filled with argon and sealed with an aluminum/Teflon crimp top. The reaction mixture was then irradiated for 1 h at 120° C., using an irradiation power of 100 W. After completion of the reaction, the vial was cooled to 50° C. with air jet cooling before it was opened. The reaction mixture was diluted with EtOAc and filtered on a pad of Solca Floc®200FCC. The crude product was purified by flash chromatography eluting with 5-100% EtOAc/petroleum ether affording the titled compound as yellow oil. 1H-NMR (400 MHz, DMSO-d6, 300K) δ 7.59 (1H, d, J=5.1 Hz), 7.04 (1H, d, J=5.1 Hz), 5.42 (2H, br. s), 2.24-2.15 (1H, m), 0.92-0.82 (4H, m). MS (ES) C8H9ClN2 requires: 168, found: 169, 171 (M+H)+.

Workup

  1. customequipped with a small magnetic stirring bar
  2. customThe reaction vessel was fitted with a rubber septum
  3. customwas evacuated
  4. additionback-filled with argon
  5. customsealed with an aluminum/Teflon crimp top
  6. customThe reaction mixture was then irradiated for 1 h at 120° C.
  7. customAfter completion of the reaction
  8. temperaturecooling before it
  9. filtrationfiltered on a pad of Solca Floc®200FCC
  10. customThe crude product was purified by flash chromatography
  11. washeluting with 5-100% EtOAc/petroleum ether affording the titled compound as yellow oil

Sources & evidence

ORD record
ord-12aa4245215c4604b5795fa549e1a0df
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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