Ammonium Chloride → N-(4-Methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amine

HRID 1670202Notes

Reaction equation

HRID 1670202 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=3[F:25])[N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[Cl-].[NH4+]>[Zn].CO.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=3[F:25])[N:12]=[CH:11][N:10]=2)=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 593016056-(2-Fluoro-4-nitrophenoxy)-N-(4-methoxybenzyl)pyrimidin-4-amine

Product 1

HCID 59301603N-(4-Methoxybenzyl)-6-(4-amino-2-fluorophenoxy)pyrimidin-4-amineYield 103.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of N-(4-methoxybenzyl)-6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-amine (150 mg, 0.41 mmol) in 1:1 MeOH/THF (20 mL) was treated with ammonium chloride (0.22 g, 4.1 mmol), and zinc dust (<20 microns, 0.27 g, 4.2 mmol). The reaction mixture was stirred at RT for 1 h. An additional portion of zinc dust (150 mg) was added to the mixture and the reaction mixture was stirred at RT for 1 h and heated at 70° C. for 20 min. The mixture was filtered to remove the inorganic solids, concentrated in vacuo, and the residue partitioned between EtOAc and brine. The EtOAc phase was separated, washed with brine, dried (MgSO4) and concentrated in vacuo to give the title compound (145 mg, 99%). 1H NMR (DMSO-d6) δ 8.10 (br s, 1H), 7.76 (br s, 1H), 7.21 (d, 2H, J=8.6 Hz), 6.88 (d, 3H, J=8.6 Hz), 6.44 (dd, 1H, J=12.7, 2.0 Hz), 6.36 (dd, 1H, J=8.3, 2.3 Hz), 5.79 (s, 1H), 4.41 (br s, 2H), 3.73 (s, 3H); MS (ESI+) m/z 341.18 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. temperatureheated at 70° C. for 20 min
  3. filtrationThe mixture was filtered
  4. customto remove the inorganic solids
  5. concentrationconcentrated in vacuo
  6. customthe residue partitioned between EtOAc and brine
  7. customThe EtOAc phase was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-00f04154febb42ce82596570496a2a87
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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