Sodium thiocyanate → HCID 178439361, compound

HRID 347511Notes

Reaction equation

HRID 347511 reaction equation
[S-:1][C:2]#[N:3].[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13](Cl)=[O:14])=[CH:8][CH:7]=1.[F:16][C:17]1[CH:18]=[C:19]([NH2:36])[CH:20]=[CH:21][C:22]=1[O:23][CH:24]1[C:29]2=[C:30]([CH:33]([CH3:35])[CH3:34])[CH:31]=[CH:32][N:28]2[N:27]=[CH:26][NH:25]1.C1COCC1.ClCCl>C(OCC)(=O)C>[F:16][C:17]1[CH:18]=[C:19]([NH:36][C:2]([NH:3][C:13](=[O:14])[CH2:12][C:9]2[CH:10]=[CH:11][C:6]([F:5])=[CH:7][CH:8]=2)=[S:1])[CH:20]=[CH:21][C:22]=1[O:23][CH:24]1[C:29]2=[C:30]([CH:33]([CH3:34])[CH3:35])[CH:31]=[CH:32][N:28]2[N:27]=[CH:26][NH:25]1

Participants

6

Reactant 4

HCID 516871Sodium thiocyanateHCID 37449884-Fluorophenylacetyl chlorideHCID 21919333Tetrahydrofurane dichloromethaneHCID 178439360HCID 178439360, compound

Product 1

HCID 178439361HCID 178439361, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a homogeneous solution of sodium thiocyanate (0.037 g, 0.46 mmol, 3.3 equiv) in ethyl acetate (1 mL), at room temperature under a nitrogen atmosphere, was added 4-fluorophenyl-acetyl chloride (0.048 ml, 0.35 mmol, 2.5 equiv). The mixture was stirred for 2 h before being added directly to a homogeneous solution of 3-fluoro-4-(5-isopropyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine (0.040 g, 0.139 mmol, 1.0 equiv) in anhydrous 1/1 THF/dichloromethane (3 mL), under a nitrogen atmosphere. The reaction mixture was stirred at ambient temperature for 16 h before being quenched with 1 N HCl. The solution was extracted with CH2Cl2 (3×50 ml), the combined organic fractions washed with 1 N NaOH (50 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography, eluting with 4/1 hexane/ethyl acetate, afforded the title compound (0.050 g, 75%). 1H NMR (CDCl3) δ 12.34 (s, 1H), 8.47 (m, 1H), 7.65–7.78 (m, 2H), 7.63–7.64 (m, 1H), 7.19–7.32 (m, 4H) 703–7.08 (m, 2H), 6.66–6.67 (m, 1H), 3.65 (s, 2H), 3.40–3.50 (m, 1H), 1.28–1.30 (m, 6H); HRMS(ESI) 482.1462, calc, (M+H)+ 482.1461 found. Elemental Analysis: C24H21N5O2SF2. 0.23 H2O. calc: C, 59.35; H, 4.45, N, 14.42, found. C, 59.36; H, 4.44; N, 14.03.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 16 h
  2. custombefore being quenched with 1 N HCl
  3. extractionThe solution was extracted with CH2Cl2 (3×50 ml)
  4. washthe combined organic fractions washed with 1 N NaOH (50 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography
  9. washeluting with 4/1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-42a803a415604e188c1d4e636e640d28
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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