HCID 66617855, compound → HCID 86634767, compound

HRID 911050Notes

Reaction equation

HRID 911050 reaction equation
[Cl:1][C:2]1[C:7]([N:8]=[C:9]=[S:10])=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1.[F:12][C:13]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:14]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[CH:17]=1>CN(C=O)C>[ClH:1].[F:12][C:13]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:14]=1[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:9]2[S:10][C:2]3[C:7]([N:8]=2)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=3)[CH:17]=1

Participants

4

Reactant 2

HCID 66617855HCID 66617855, compoundHCID 83290701HCID 83290701, compound

Product 1

HCID 86634767HCID 86634767, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-3-isothiocyanato-6-methylpyridine (0.0831 g, 0.450 mmol) and 4-(2,6-difluorophenoxy)pyridin-2-amine (0.100 g, 0.450 mmol) in DMF (2 mL) was stirred at 80° C. for 3 hours and then at 120° C. overnight. The reaction was cooled and partitioned between ethyl acetate and 2N NaOH. The organic layer was washed with water and brine, dried, and concentrated. The crude material was purified via MPLC (Biotage) eluting with 3:2 hexane:ethyl acetate. The isolated product was dissolved in ether (5 mL), followed by the addition of 1N HCl in ether (3 mL) and then hexanes (4 mL). The resulting solids were filtered and washed with hexanes to provide the desired product (0.095 g, 51.9% yield) as a white powder: 1H NMR (d6-DMSO) δ 2.64 (s, 3H), 6.71 (s, 1H), 6.81 (d, 1H), 7.38-7.53 (m, 4H), 8.05 (d, 1H), 8.36 (d, 1H).

Workup

  1. customat 120° C.
  2. customovernight
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and 2N NaOH
  5. washThe organic layer was washed with water and brine
  6. customdried
  7. concentrationconcentrated
  8. customThe crude material was purified via MPLC (Biotage)
  9. washeluting with 3:2 hexane
  10. dissolutionThe isolated product was dissolved in ether (5 mL)
  11. additionfollowed by the addition of 1N HCl in ether (3 mL)
  12. filtrationThe resulting solids were filtered
  13. washwashed with hexanes

Sources & evidence

ORD record
ord-9abbd86f6479403abb41450c3f156321
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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