Cesium carbonate → HCID 86731666, compound

HRID 1504773Notes

Reaction equation

HRID 1504773 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([CH3:12])[N:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:61][O:62][C:63]1[CH:70]=[C:69]([O:71][CH3:72])[CH:68]=[CH:67][C:64]=1[CH2:65][NH2:66]>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].O1CCOCC1>[CH3:61][O:62][C:63]1[CH:70]=[C:69]([O:71][CH3:72])[CH:68]=[CH:67][C:64]=1[CH2:65][NH:66][C:2]1[CH:7]=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([CH3:12])[N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5972502,4-DimethoxybenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86731667HCID 86731667, compound

Product 1

HCID 86731666HCID 86731666, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A flask containing a mixture of 2-(2-chloro-6-methylpyridin-4-yl)propan-2-ol (303 mg, 1.63 mmol), tris(dibenzylideneacetone)dipalladium(0) (149 mg, 0.163 mmol), Xantphos (189 mg, 0.326 mmol), and cesium carbonate (798 mg, 2.45 mmol) was purged with argon for 5 minutes. To this mixture was added 2,4-dimethoxybenzylamine (0.983 mL, 6.53 mmol) and 1,4-dioxane (7 mL). The reaction mixture was purged with argon for 5 minutes, and then heated to 100° C. After 4 hours, the reaction mixture was cooled, diluted with ethyl acetate (50 mL), filtered through CELITE, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes, linear gradient) to afford 2-{2-[(2,4-dimethoxybenzyl)amino]-6-methylpyridin-4-yl}propan-2-ol. MS ESI calc'd. for C18H25N2O3 [M+H]+ 317. found 317. 1H NMR (500 MHz, DMSO-d6) δ 7.12 (d, J=8.5 Hz, 1H), 6.51 (d, J=2.5 Hz, 1H), 6.44-6.40 (m, 2H), 6.38 (d, J=7.0 Hz, 2H), 4.90 (s, 1H), 4.30 (d, J=5.5 Hz, 2H), 3.78 (s, 3H), 3.71 (s, 3H), 2.19 (s, 3H), 1.29 (s, 6H).

Workup

  1. additionA flask containing
  2. customwas purged with argon for 5 minutes
  3. customThe reaction mixture was purged with argon for 5 minutes
  4. temperaturethe reaction mixture was cooled
  5. additiondiluted with ethyl acetate (50 mL)
  6. filtrationfiltered through CELITE
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-2f185b6329b9411a8cc6cd247e9a8aa6
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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