4-Aminotetrahydropyran → HCID 42630021, compound

HRID 548894Notes

Reaction equation

HRID 548894 reaction equation
C[Al](C)C.[NH2:5][CH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C([O:14][C:15]([C:17]1[N:18]=[N:19][C:20]([O:23][CH2:24][C:25]2[C:26]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)=[N:27][O:28][C:29]=2[CH3:30])=[CH:21][CH:22]=1)=O)C.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCOCC1>[O:9]1[CH2:10][CH2:11][CH:6]([NH:5][C:15]([C:17]2[N:18]=[N:19][C:20]([O:23][CH2:24][C:25]3[C:26]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=4)=[N:27][O:28][C:29]=3[CH3:30])=[CH:21][CH:22]=2)=[O:14])[CH2:7][CH2:8]1

Participants

6

Reactant 4

HCID 4192234-AminotetrahydropyranHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 42630371HCID 42630371, compound

Product 1

HCID 42630021HCID 42630021, compoundYield 52.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 600 μL, 1.2 mmol) was added dropwise (exothermic) to a solution of 4-aminotetrahydropyran (121 mg, 1.2 mmol) in dioxane (6 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-(5-methyl-3-pyridin-2-yl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid ethyl ester (102 mg, 0.3 mmol) in dioxane (3 mL) was added. The resulting mixture was heated at 85-95° C. for 5 h, cooled to room temperature, poured into a sodium potassium tartrate solution and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (62 mg, 52%) which was obtained as a white solid after recrystallisation from ethylacetate:heptane. MS: m/e=396.3 [M+H]+.

Workup

  1. temperatureThe resulting mixture was heated at 85-95° C. for 5 h
  2. temperaturecooled to room temperature
  3. extractionextracted with ethyl acetate which
  4. washwas then washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1)

Sources & evidence

ORD record
ord-ec85cffedb1c4cb49b1e153fe1195193
Source dataset
uspto-grants-2011_05
Patent number
US07943619B2

Reaction notes

Loading…