Tetrahydrofuran → HCID 21081663, compound

HRID 2117149Notes

Reaction equation

HRID 2117149 reaction equation
Br[CH2:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][C:12]=2[O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][C:16]=2[F:24])[NH:7][CH:6]=1)=O.[NH2:25][C:26]([NH2:28])=[S:27].C1COCC1.[Cl-].[NH4+]>C(O)(=O)C.CCOC(C)=O.[Zn].CO>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][C:12]2[CH:11]=[CH:10][N:9]=[C:8]3[NH:7][CH:6]=[C:5]([C:3]4[N:25]=[C:26]([NH2:28])[S:27][CH:2]=4)[C:13]=23)=[C:16]([F:24])[CH:17]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 2723790ThioureaHCID 21081562HCID 21081562, compound

Product 1

HCID 21081663HCID 21081663, compound

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 2-bromo-1-(4-(2-fluoro-4-nitrophenoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone (392 mg, 1.0 mmol) in acetic acid (10 mL) was added thiourea (228 mg, 3.0 mmol, Aldrich). The reaction mixture was stirred at room temperature for 3 h, and then diluted with 50 mL of EtOAc. The reaction mixture was washed with saturated aq. NaHCO3 solution and brine. The organic layer was dried (MgSO4) and concentrated in vacuo to give a light yellow solid. The solid was dissolved in a mixed solvent (20 mL of THF and 40 mL of MeOH). Ammonium chloride (267 mg, 5.0 mmol, EMD) and Zn dust (327 mg, 5.0 mmol, Aldrich) were added then added to the resulting solution. The reaction mixture was stirred at room temperature overnight, diluted with 100 mL of EtOAc and filtered through a pad of Celite®. The filtrate was concentrated in vacuo and the resulting residue was purified by preparative HPLC. The desired fractions were combined, neutralized with saturated aq. NaHCO3 solution, and concentrated under reduced pressure. The solid that formed was collected by filtration (194 mg, 57% over two steps). MS(ESI+) m/z 342.2 (M+H)+.

Workup

  1. washThe reaction mixture was washed with saturated aq. NaHCO3 solution and brine
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give a light yellow solid
  5. additionthen added to the resulting solution
  6. stirringThe reaction mixture was stirred at room temperature overnight
  7. filtrationfiltered through a pad of Celite®
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe resulting residue was purified by preparative HPLC
  10. concentrationconcentrated under reduced pressure
  11. customThe solid that formed
  12. filtrationwas collected by filtration (194 mg, 57% over two steps)

Sources & evidence

ORD record
ord-9eb63eab437948dfa7c97d8d0efd1b9b
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

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