2-(4-Fluorophenyl)acetyl isothiocyanate → N-(3-Fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-(4-fluorophenyl)acetamide

HRID 1047426Notes

Reaction equation

HRID 1047426 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]=[C:12]=[S:13])=[O:10])=[CH:4][CH:3]=1.[O:14]1CCCO[CH:15]1[C:20]1[CH:21]=[CH:22][C:23]([C:26]2[S:34][C:33]3[C:28](=[N:29][CH:30]=[CH:31][C:32]=3[O:35][C:36]3[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][C:37]=3[F:43])[CH:27]=2)=[N:24][CH:25]=1.[N-]=C=S>C1(C)C=CC=CC=1.C(O)C.C(O)C.C1(C)C=CC=CC=1.C(O)(=O)C>[F:43][C:37]1[CH:38]=[C:39]([NH:40][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[S:13])[CH:41]=[CH:42][C:36]=1[O:35][C:32]1[CH:31]=[CH:30][N:29]=[C:28]2[CH:27]=[C:26]([C:23]3[CH:22]=[CH:21][C:20]([CH:15]=[O:14])=[CH:25][N:24]=3)[S:34][C:33]=12

Participants

8

Reactant 3

HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 579672584-(2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroanilineHCID 178418790HCID 178418790, compound

Product 1

HCID 25212245N-(3-Fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenylcarbamothioyl)-2-(4-fluorophenyl)acetamideYield 72%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 1140TolueneSolvent2×HCID 21863594Toluene ethanolSolvent

Procedure

To a solution of 2 (5.27 g, 27.0 mmol) in toluene (50.0 mL) and ethanol (50.0 mL) was added a suspension of intermediate 31 (9.52 g, 22.5 mmol) in toluene (20 mL) and ethanol (20 mL) over 30 min. After few minutes, more of isothiocyanate (1 g) in ethanol/toluene (5 mL/5 mL) mixture was added over 1 min. The reaction mixture was stirred at r.t. for an additional 30 min and concentrated under reduced pressure. The residue was triturated with toluene (70 mL), filtered and washed with toluene (20 mL) to afford a beige solid material that was suspended in 80% acetic acid (204 mL) and heated at 90° C. overnight. The reaction mixture was cooled down to r.t., and the precipitate was collected by filtration, washed with 80% AcOH (2×30 mL) to afford compound 33 (8.24 g, 72% yield) as a yellow solid.

Workup

  1. waitAfter few minutes
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was triturated with toluene (70 mL)
  4. filtrationfiltered
  5. washwashed with toluene (20 mL)
  6. customto afford a beige solid material that
  7. temperatureheated at 90° C. overnight
  8. temperatureThe reaction mixture was cooled down to r.t.
  9. filtrationthe precipitate was collected by filtration
  10. washwashed with 80% AcOH (2×30 mL)

Sources & evidence

ORD record
ord-3f20bcb7a6ca418aa30a2baa7e1f3d40
Source dataset
uspto-grants-2013_10
Patent number
US08569503B2

Reaction notes

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