Cesium carbonate → HCID 70873881, compound

HRID 2208881Notes

Reaction equation

HRID 2208881 reaction equation
C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.[O:47]1[CH2:52][CH2:51][CH:50]([NH2:53])[CH2:49][CH2:48]1.Cl[C:55]1[C:60]([CH3:61])=[C:59]([C:62]([O:64][CH3:65])=[O:63])[CH:58]=[CH:57][N:56]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:61][C:60]1[C:55]([NH:53][CH:50]2[CH2:51][CH2:52][O:47][CH2:48][CH2:49]2)=[N:56][CH:57]=[CH:58][C:59]=1[C:62]([O:64][CH3:65])=[O:63]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 4192234-AminotetrahydropyranHCID 634876Binap, (A+-)-HCID 53436889Methyl 2-chloro-3-methylpyridine-4-carboxylate

Product 1

HCID 70873881HCID 70873881, compoundYield 39%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
40 °C

Procedure

A nitrogen purged suspension of Pd(OAc)2 (77 mg, 0.34 mmol) and 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (430 mg, 0.69 mmol) in 1,4-dioxane (11 ml) was heated at 40° C. for 1 hour. Oxan-4-amine (237 μl, 2.3 mmol), a solution of methyl 2-chloro-3-methylpyridine-4-carboxylate (213 mg, 1.2 mmol) in degassed dioxane (2 ml) and Cs2CO3 (562 mg, 1.7 mmol) were then added and the red suspension was heated at 100° C. for 6 hours. After cooling to room temperature, the mixture was diluted with CH2Cl2 (30 ml) and water (20 ml). The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×15 ml). The combined organic phases were washed with brine (25 ml), dried (MgSO4), filtered and concentrated in-vacuo. The crude residue was purified by column chromatography (25 g SNAP cartridge, Isolera, 0-28% ethyl acetate:heptanes) followed by prep-HPLC (MeCN/Water) to give the title compound (112 mg, 39%) as a white crystalline solid. LC-MS 100%, m/z=251.0; 1H NMR (500 MHz, MeOD) δ ppm 7.91 (d, J=5.20 Hz, 1H) 6.77 (d, J=5.36 Hz, 1H) 4.07-4.17 (m, 1H) 3.98 (dd, J=12.06, 1.81 Hz, 2H) 3.88 (s, 3H) 3.55 (td, J=11.78, 1.66 Hz, 2H) 2.22 (s, 3H) 1.97 (dd, J=12.69, 1.97 Hz, 2H) 1.62 (qd, J=12.03, 4.41 Hz, 2H). NH not observed.

Workup

  1. customA nitrogen purged
  2. temperaturethe red suspension was heated at 100° C. for 6 hours
  3. temperatureAfter cooling to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with CH2Cl2 (3×15 ml)
  6. washThe combined organic phases were washed with brine (25 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in-vacuo
  10. customThe crude residue was purified by column chromatography (25 g SNAP cartridge, Isolera, 0-28% ethyl acetate:heptanes)

Sources & evidence

ORD record
ord-26d8d5c333d245dabb03066f1d029257
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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