Ammonia → HCID 86622898, compound

HRID 643512Notes

Reaction equation

HRID 643512 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:22]=[CH:23][CH:24]=2)[O:12][CH2:13][C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=1.CCO.[NH3:28].[NH4+].[Cl-]>C(Cl)(Cl)Cl.C(OCC)C>[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:22]=[CH:23][CH:24]=2)[O:12][CH2:13][C:14]2[CH:21]=[CH:20][C:17]([C:18]([NH2:28])=[NH:19])=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 222Ammonia2×HCID 702EthanolHCID 25517Ammonium ChlorideHCID 714221424-({3-[(2-Chloropyrimidin-4-yl)oxy]phenoxy}methyl)benzonitrile

Product 1

HCID 86622898HCID 86622898, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6212ChloroformSolvent

Procedure

4-[3-(2-Chloro-pyrimidin-4-yloxy)-phenoxymethyl]-benzonitrile (169 mg; 0.5 mmol; Example 6; Stage 6.1) is dissolved in CHCl3 (5 mL) and EtOH (0.5 mL) and cooled to 0° C. At this temperature, HCl gas is gently bubbled through during 20 min. The reaction mixture is kept at 4-5° C. for 72 h. After this time, pentane (10 mL) is added and stirring is continued for 1 h at 0° C. The supernatant is removed by decantation, and the residue (intermediate product) is suspended in MeOH (2 mL). At 0° C., NH3 (0.375 mL 2M solution in MeOH; 0.75 mmol) and NH4Cl (27 mg; 0.5 mmol) are added and the mixture is stirred at rt for 5 h 15 min. More NH3 (0.375 mL 2M solution in MeOH; 0.75 mmol) is added, as well as diethyl ether. After removal of the solvents under reduced pressure, the residue is taken up in EtOAc/water, extracted with water and brine and dried (Na2SO4). After filtration, the solvent is removed under reduced pressure to obtain a small amount of the title compound as free base. Since most of the product is in the aqueous layer, the latter is lyophilized and the residue purified twice over reversed phase silica (Lichroprep RP18; 15-25 μm), eluting with H2O/acetonitrile (0->43%) (0.1% TFA in both). After concentration of the solution, the title compound is isolated by lyophilization as TFA salt; ES-MS: [M+H]+; m/z=355; HPLC: AtRet=3.43 min.

Workup

  1. customAt this temperature, HCl gas is gently bubbled through during 20 min
  2. additionAfter this time, pentane (10 mL) is added
  3. waitis continued for 1 h at 0° C
  4. customThe supernatant is removed by decantation
  5. stirringthe mixture is stirred at rt for 5 h 15 min
  6. customAfter removal of the solvents under reduced pressure
  7. extractionextracted with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationAfter filtration
  10. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-79ebb5eab75b4f638809167ea0fd5356
Source dataset
uspto-grants-2010_04
Patent number
US07700605B2

Reaction notes

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