Sodium thiocyanate → 1-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)-acetyl)thiourea

HRID 347485Notes

Reaction equation

HRID 347485 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]([NH2:33])[CH:20]=[CH:21][C:22]=1[O:23][C:24]1[C:29]2=[CH:30][CH:31]=[CH:32][N:28]2[N:27]=[CH:26][N:25]=1>C(OCC)(=O)C.ClCCl>[F:16][C:17]1[CH:18]=[C:19]([NH:33][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][C:24]1[C:29]2=[CH:30][CH:31]=[CH:32][N:28]2[N:27]=[CH:26][N:25]=1

Participants

6

Reactant 3

HCID 516871Sodium thiocyanateHCID 37449884-Fluorophenylacetyl chlorideHCID 210816213-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine2×

Product 1

HCID 116478491-(3-Fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)-acetyl)thioureaYield 83.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a homogeneous solution of sodium thiocyanate (21 mg, 0.26 mmol) in ethyl acetate (1 mL), at room temperature under a nitrogen atmosphere, was added 4-fluorophenyl-acetyl chloride (28 μL, 0.20 mmol). The mixture was stirred for 30 minutes before being added directly to a homogeneous solution of 3-fluoro-4-(pyrrolo[2,1-f][1,2,4]-triazin-4-yloxy)benzenamine (37 mg, 0.15 mmol, Compound C of Example 22) in anhydrous dichloromethane (3 mL), under a nitrogen atmosphere. The mixture was stirred at ambient temperature for 4 h before being concentrated in vacuo. Purification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography, eluting with chloroform, afforded the title compound (55 mg, 83%). 1H NMR (CDCl3) δ 12.41 (s, 1H), 8.50 (s, 1H), 7.97 (s, 1H), 7.92 (m, 1H), 7.81 (m, 1H), 7.42 (m, 1H), 7.35–725 (m, 3H), 7.17–7.10 (m, 2H), 705–7.02 (m, 1H), 6.85–6.90 (m, 1H), 3.72 (s, 2H); HRMS(ESI), 440.0993 (M+H)+ calc, 440.0988 (M+H)+ found.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 4 h
  2. concentrationbefore being concentrated in vacuo
  3. customPurification by silica gel (Merck KGaA, 230–400 mesh particle size) flash chromatography
  4. washeluting with chloroform

Sources & evidence

ORD record
ord-050b5be5324c4783a26c4c0e01c7b869
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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