Ammonium Chloride → (7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)(4-methylpiperazin-1-yl)methanone

HRID 1400946Notes

Reaction equation

HRID 1400946 reaction equation
[F:1][C:2]1[CH:26]=[C:25]([N+:27]([O-])=O)[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[O:15])[S:13][C:6]=12.[Cl-].[NH4+]>CO.O.[Zn]>[NH2:27][C:25]1[CH:24]=[CH:23][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[O:15])[S:13][C:6]=23)=[C:2]([F:1])[CH:26]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 58474693(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)(4-methylpiperazin-1-yl)methanone

Product 1

HCID 58474542(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)(4-methylpiperazin-1-yl)methanoneYield 66%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Zinc (0.75 g, 11.53 mmol) was added to a suspension of 437 (1.2 g, 2.88 mmol) and ammonium chloride (0.31 g, 5.76 mmol) in a mixture of MeOH (30 mL) and water (5.10 mL). The suspension was heated to reflux for 50 min. After cooling to room temperature, the reaction mixture was filtered and concentrated. The residue was partitioned between DCM, water and ammonium hydroxide. The organic layer was collected, successively washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by biotage (SNAP 50 g cartridge; MeOH/DCM: 0/100 to 20/80 over 30CV), to afford the title compound 438 (733 mg, 1.89 mmol, 66% yield) as a yellow solid. MS (m/z): 387.4 (M+H).

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 50 min
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated
  5. customThe residue was partitioned between DCM, water and ammonium hydroxide
  6. customThe organic layer was collected
  7. washsuccessively washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by biotage (SNAP 50 g cartridge; MeOH/DCM: 0/100 to 20/80 over 30CV)

Sources & evidence

ORD record
ord-7fcddb8e823c47d7a663f75284d4d132
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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