Lithium Chloride → 6-{(E)-2-[3-tert-butyl-5-(5-fluoro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-pyridin-3-ylamine

HRID 2390866Notes

Reaction equation

HRID 2390866 reaction equation
O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[C:17]([C:21]1[CH:22]=[C:23]([C:44]2[C:45]([O:51][CH3:52])=[N:46][CH:47]=[C:48]([F:50])[CH:49]=2)[CH:24]=[C:25](/[CH:29]=[CH:30]/[Sn](CCCC)(CCCC)CCCC)[C:26]=1[O:27][CH3:28])([CH3:20])([CH3:19])[CH3:18].I[C:54]1[CH:59]=[CH:58][C:57]([NH2:60])=[CH:56][N:55]=1.[Cl-].[Li+]>CN(C=O)C.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].O>[C:17]([C:21]1[C:26]([O:27][CH3:28])=[C:25](/[CH:29]=[CH:30]/[C:54]2[N:55]=[CH:56][C:57]([NH2:60])=[CH:58][CH:59]=2)[CH:24]=[C:23]([C:44]2[C:45]([O:51][CH3:52])=[N:46][CH:47]=[C:48]([F:50])[CH:49]=2)[CH:22]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

8

Reactant 4

HCID 433294Lithium ChlorideHCID 521585Tris(furan-2-yl)phosphaneHCID 23205766-Iodopyridin-3-amineHCID 591566343-[3-tert-Butyl-4-methoxy-5-((E)-2-tributylstannanyl-vinyl)-phenyl]-5-fluoro-2-methoxy-pyridine

Product 1

HCID 672865546-{(E)-2-[3-tert-butyl-5-(5-fluoro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-pyridin-3-ylamineYield 87.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
110 °C

Procedure

step 1—A solution of Pd2(dba)3 (27.8 mg, 0.030 mmol) and tris-(2-furyl)phosphine (28.0 mg, 0.121 mmol) in anhydrous DMF (3 mL) was stirred at RT for 15 min under argon. To the resulting solution was added via cannula a solution of 364 (672 mg, 1.11 mmol) and 2-iodo-5-aminopyridine (294 mg, 1.33 mmol) in anhydrous DMF (6 mL) at RT. Lithium chloride (97.1 mg, 2.23 mmol) was then added under argon. The reaction mixture was heated at 110° C. for 18 h. After cooling to RT, the reaction mixture was poured into H2O (90 mL) and thrice extracted with EtOAc (60 mL). The combined extracts were washed with H2O (130 mL) and brine (130 mL), dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (37 to 100% EtOAc) to afford 0.394 g (85%) of 6-{(E)-2-[3-tert-butyl-5-(5-fluoro-2-methoxy-pyridin-3-yl)-2-methoxy-phenyl]-vinyl}-pyridin-3-ylamine (370).

Workup

  1. temperatureAfter cooling to RT
  2. extractionextracted with EtOAc (60 mL)
  3. washThe combined extracts were washed with H2O (130 mL) and brine (130 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by SiO2 chromatography
  8. washeluting with an EtOAc/hexane gradient (37 to 100% EtOAc)

Sources & evidence

ORD record
ord-42ea3b71795c45409c2aecd0923e8963
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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