Tetrahydrofuran → 5-Morpholinopyridin-2-amine

HRID 868830Notes

Reaction equation

HRID 868830 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1>C(O)(C)(C)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>[N:9]1([C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=2)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 706222-Amino-5-bromopyridineHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 113673465-Morpholinopyridin-2-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

A solution of 2-amino-5-bromopyridine (2.0 g, 0.011 mol) in t-butanol (5 ml) is degassed with nitrogen for 5 min. Morpholine (1.4 g, 0.016 mol), Davephos (0.4 g, 0.001 mol) and tris(dibenzylideneacetone)dipalladium(0) (0.25 g, 0.027 mmol) is added. A 1.6M solution of lithium bis(trimethylsilyl)amide in THF (5.51 g, 0.033 mol) is then added dropwise. The reaction mixture is irradiated in the microwave at 150° C. for 2 h. Water is added (30 ml), and the mixture is extracted with ethyl acetate (2×100 ml). The organic phases are washed with water (1×100 ml) and dried over sodium sulfate. The crude material is employed in the next step without purification. 5-Morpholin-4-ylpyridin-2-ylamine is employed in the synthesis of “A7”.

Workup

  1. customThe reaction mixture is irradiated in the microwave at 150° C. for 2 h
  2. extractionthe mixture is extracted with ethyl acetate (2×100 ml)
  3. washThe organic phases are washed with water (1×100 ml)
  4. dry with materialdried over sodium sulfate
  5. customThe crude material is employed in the next step without purification
  6. custom5-Morpholin-4-ylpyridin-2-ylamine is employed in the synthesis of “A7”

Sources & evidence

ORD record
ord-313f4f1a639f4d7e83a95644090d721d
Source dataset
uspto-grants-2015_03
Patent number
US08969335B2

Reaction notes

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