Triethylamine → HCID 59255192, compound

HRID 1694093Notes

Reaction equation

HRID 1694093 reaction equation
[N+:1]([CH2:4][CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=1)([O-:3])=O.C[O-].[Li+].C(=O)([O-])O.[Na+].[C:27]([C:29]1[C:30]([NH2:36])=[N:31][C:32]([NH2:35])=[CH:33][CH:34]=1)#[CH:28].C(N(CC)CC)C>[Ti](Cl)(Cl)(Cl)Cl.O.O1CCCC1.CO>[O:12]([C:10]1[CH:11]=[C:6]([CH2:5][C:4]2[CH:28]=[C:27]([C:29]3[C:30]([NH2:36])=[N:31][C:32]([NH2:35])=[CH:33][CH:34]=3)[O:3][N:1]=2)[CH:7]=[N:8][CH:9]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 4177230Lithium methanolateHCID 552816763-Ethynylpyridine-2,6-diamineHCID 592554813-(2-Nitroethyl)-5-phenoxypyridine

Product 1

HCID 59255192HCID 59255192, compoundYield 14.2%

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a methanol (5 mL) solution of 3-(2-nitro-ethyl)-5-phenoxy-pyridine (210 mg, 0.860 mmol) described in Manufacturing Example 145-1-4 was added lithium methoxide (65 mg, 1.72 mmol), which was stirred for 25 minutes at room temperature. The reaction mixture was concentrated under a reduced pressure. To a suspension of this residue in tetrahydrofuran (5 mL) ad methylene chloride (5 mL) was added titanium (IV) tetrachloride (236 μL, 2.15 mmol) under nitrogen atmosphere, which was stirred for 50 minutes at 0° C. Sodium hydrogencarbonate was added to the reaction mixture at 0° C., which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. To a tetrahydrofuran (4 mL) solution of this residue were added 3-ethynyl-pyridin-2,6-diamine (15 mg, 0.11 mmol) described in Manufacturing Example 13-1-3 and triethylamine (240 μL, 1.72 mmol), which was stirred for 1 hour and 15 minutes at 50° C. Water was added to the reaction mixture at room temperature, which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain the title compound (5.6 mg, 1.1%) as a ditrifluoroacetic acid salt.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. additionTo a suspension of this residue in tetrahydrofuran (5 mL) ad methylene chloride (5 mL)
  3. stirringwhich was stirred for 50 minutes at 0° C
  4. extractionwhich was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under a reduced pressure
  10. stirringwas stirred for 1 hour and 15 minutes at 50° C
  11. extractionwhich was extracted with ethyl acetate
  12. customThe organic layer was separated
  13. washwashed with saturated aqueous sodium chloride
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. concentrationThe filtrate was concentrated under a reduced pressure
  17. customthe residue was purified by reverse-phase high performance liquid chromatography (
  18. additioncontaining 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-b1705cf84f3948759d38e70b619a1513
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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