Phosphorus trichloride → HCID 178422966, compound

HRID 2227160Notes

Reaction equation

HRID 2227160 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[N:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]([OH:15])=O.[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][NH2:22])=[CH:19][CH:18]=1.P(Cl)(Cl)Cl>O>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][NH:22][C:13]([C:3]2[CH:4]=[N:5][C:6]3[C:11]([C:2]=2[OH:1])=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=3)=[O:15])=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 24387Phosphorus trichlorideHCID 660364-ChlorobenzylamineHCID 178422970HCID 178422970, compound

Product 1

HCID 178422966HCID 178422966, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxylic acid (0.204 g) and 4-chlorobenzylamine (0.12 mL) is heated to reflux. To this is added dropwise phosphorus trichloride (0.04 mL). Refluxing is continued for 3 h. The mixture is cooled and water is added to destroy excess PCl3. The solvents are removed. The residue is partitioned between EtOAc and water. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are washed with brine (1×), dried and condensed. The residue is adsorbed on silica and chromatographed (eluent 5% MeOH/CH2Cl2). Fractions homogeneous by TLC are condensed and triturated with Et2O/hexanes to yield 0.017 g (5%) of the desired product as a yellow solid. Physical characteristics are as follows: m.p. 280-285° C. (dec); 1H NMR (300 MHz, DMSO) δ 13.0, 10.20, 8.63, 8.47, 7.38, 4.52, 2.61; IR (mull) 3186, 3148, 3055, 3034, 1655, 1605, 1570, 1546, 1494, 1333, 1243, 1097, 814, 799, 623 cm−1; MS (EI) m/z 327 (M+), 188, 187, 161, 160, 142, 140, 132, 131, 104; HRMS (EI) calcd for C17H14ClN3O2 327.0775, found 327.0783.

Workup

  1. temperatureRefluxing
  2. temperatureThe mixture is cooled
  3. customto destroy excess PCl3
  4. customThe solvents are removed
  5. customThe residue is partitioned between EtOAc and water
  6. extractionThe aqueous layer is extracted with EtOAc (3×)
  7. washThe combined organic layers are washed with brine (1×)
  8. customdried
  9. customcondensed
  10. customchromatographed (eluent 5% MeOH/CH2Cl2)
  11. customcondensed
  12. customtriturated with Et2O/hexanes

Sources & evidence

ORD record
ord-f07c18a3603c46dca8aa12a699b47772
Source dataset
uspto-grants-2002_07
Patent number
US06413958B2

Reaction notes

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