1-Hydroxybenzotriazole → HCID 86592800, compound

HRID 1372728Notes

Reaction equation

HRID 1372728 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([F:14])[CH:3]=1.[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([C:24]([OH:26])=O)=[N:16]1.[CH:27]1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C.Cl>[Cl:8][C:7]1[C:2]([NH:1][C:24]([C:17]2[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[S:15][N:16]=2)=[O:26])=[CH:3][C:4]([F:14])=[C:5]([CH2:9][C:10]([O:12][CH2:13][CH3:27])=[O:11])[CH:6]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 945121,2-Benzisothiazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17859508HCID 17859508, compound

Product 1

HCID 86592800HCID 86592800, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 4-amino-5-chloro-2-fluorophenylacetate (753 mg, 3.25 mmol), benzo(d)isothiazole-3-carboxylic acid (583 mg, 3.25 mmol), HOBt (834 mg, 6.18 mmol), EDC HCl (934 mg, 4.88 mmol) and DMAP (catalytic amount) were dissolved in DMF (16 ml). The resulting solution was stirred for 10 hours at 80° C. After cooling, the reaction mixture was poured in 1M HCl, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (middle pressure, n-hexane/ethyl acetate 9:1, 15 ml/min, φ 50×300 mm) to give ethyl (5-chloro-2-fluoro-4-((3-benzo(d)isothiazolylcarbonyl)amino)phenyl)acetate. The resulting ester was dissolved in THF/methanol (4 ml, 3:1), and to the resulting solution was added 1M NaOH (1 ml). The mixture was stirred for 18 hours at room temperature. The solvent was distilled off under reduced pressure, and the residue was poured in 1M HCl. The crystals thus precipitated were collected by filtration under reduced pressure, washed with water and dried under reduced pressure to give (5-chloro-2-fluoro-4-((3-benzo(d)isothiazolylcarbonyl)amino)phenyl)acetic acid (354 mg, 30%) as a colorless solid.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationdistilled under reduced pressure
  6. customto remove the solvent
  7. customThe residue was purified by silica gel column chromatography (middle pressure, n-hexane/ethyl acetate 9:1, 15 ml/min, φ 50×300 mm)

Sources & evidence

ORD record
ord-a1fc109ee41546caaff6c4d1bc3a5495
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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