Cesium carbonate → HCID 57795035, compound

HRID 2099569Notes

Reaction equation

HRID 2099569 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[N:23]=2)[CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1.[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32].C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.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]>[CH3:29][O:28][C:24]1[N:23]=[C:22]([CH:8]([C:4]2[N:3]=[C:2]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])[CH:7]=[CH:6][CH:5]=2)[CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57795084HCID 57795084, compound

Product 1

HCID 57795035HCID 57795035, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of enantiomer A of 2-bromo-6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridine (1.00 g, 2.235 g), methanesulfonamide (0.255 g, 2.683 mmol), Cs2CO3 (1.02 g, 3.13 mmol), Pd2(dba)3 (41 mg, 0.045 mmol), and xantphos (78 mg, 0.134 mmol) in anhydrous dioxane (10 mL) under N2 was degassed (3× pump/N2) and heated to 100° C. for 16 hr. The mixture was cooled to rt and diluted with CHCl3. The mixture was filtered through a pad of celite and washed with CHCl3 and EtOAc. The filterate was concentrated and purified by silica gel chromatography (1-5% MeOH in CH2Cl2). The mixture was then purified by acidic reverse phase HPLC (95% H20:5% CH3CN to 100% CH3CN +0.1% TFA). The fractions were concentrated then quenched with saturated aqueous. sodium bicarbonate, and extracted 3× with EtOAc. The combined organic were dried (anhd. Na2SO4), filtered and concentrated to give N-{6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide. 1H NMR (500 MHz, d6 DMSO) δ 10.43 (s, 1H), 8.64 (d, 2H, J=8.3), 8.22 (t, 2H, J =5.2), 7.91 (td, 2H, J=6.2, 1.8, 7.55-7.40 (m, 2H), 7.25-7.10 (m, 3H) 7.06 (d, 1H, J=7.3), 6.55 (d, 1H, J=7.6), 6.44 (d, 1H, J=8.1), 5.43 (d, 1H, J=12.2), 5.39 (d, 1H, J=12.2), 3.82 (s, 3H), 3.45 (s, 3H), LRMS m/z (M+H) Calcd: 462.1595, found 462.1597. Enantiomer B of N-{6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide (LRMS m/z (M+H) Calcd.: 462.1595, found 462.1597) was synthesized using the method described above except with enantiomer B of 2-bromo-6-[1-(6-methoxypyridin-2-yl)-2,2-dipyridin-3-ylethyl]pyridine.

Workup

  1. customwas degassed (3× pump/N2)
  2. temperatureThe mixture was cooled to rt
  3. additiondiluted with CHCl3
  4. filtrationThe mixture was filtered through a pad of celite
  5. washwashed with CHCl3 and EtOAc
  6. concentrationThe filterate was concentrated
  7. custompurified by silica gel chromatography (1-5% MeOH in CH2Cl2)
  8. customThe mixture was then purified by acidic reverse phase HPLC (95% H20:5% CH3CN to 100% CH3CN +0.1% TFA)
  9. concentrationThe fractions were concentrated
  10. customthen quenched with saturated aqueous
  11. extractionsodium bicarbonate, and extracted 3× with EtOAc
  12. dry with materialThe combined organic were dried (anhd. Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-f1a6e08a99834ec5adc073ec0ab056b4
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

Loading…