Potassium Hydroxide → 6-Fluoro-4-iodo-N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)pyridin-3-amine

HRID 1640908Notes

Reaction equation

OC(C(F)(F)F)=O.[F:8][C:9]1[N:14]=[CH:13][C:12]([NH2:15])=[C:11]([I:16])[CH:10]=1.Br[CH2:18][CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.[OH-].[K+].[F-].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[F:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][CH2:18][CH2:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:11]([I:16])[CH:10]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Mix 6-fluoro-4-iodopyridin-3-amine TFA salt (0.36 g, 1.50 mmol), 2-[(2-bromoethyl)oxy]tetrahydro-2H-pyran (1.38 g, 6.60 mmol), potassium hydroxide (0.19 g, 3.30 mmol), potassium fluoride (0.19 g, 3.30 mmol), and tetrabutylammonium iodide (0.11 g, 0.3 mmol) in 1,4-dioxane (1.5 mL) in a seal reactor. Heat the reaction mixture at 100° C. overnight. Cool the reaction mixture to RT. Quench with water. Extract with ethyl acetate, wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4. After filtration, concentrate and purify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2) to give the title compound (0.36 g, 66%) with 100% HPLC purity. MS (ES) m/z 367 [M+1]+.

Workup

temperatureCool the reaction mixture to RT
customQuench with water
extractionExtract with ethyl acetate
washwash the organic layer with water and saturated aqueous sodium chloride
dry with materialDry over MgSO4
filtrationAfter filtration
concentrationconcentrate
custompurify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2)

Sources & evidence

ORD record: ord-f070a66297674ab3b0d16f512f3a6f97
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08114872B2

Reaction notes

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