Glutaric anhydride → 4-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]butyric acid

HRID 459757Notes

Reaction equation

HRID 459757 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][N:7]=1.[C:21]1(=[O:28])[O:27][C:25](=[O:26])[CH2:24][CH2:23][CH2:22]1>C1(C)C=CC=CC=1>[F:20][C:19]1[CH:18]=[CH:17][C:4]([CH2:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[NH:8][N:7]=2)=[CH:3][C:2]=1[NH:1][C:21]([CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:28]

Participants

4

Reactant 2

HCID 7940Glutaric anhydrideHCID 184443734-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one

Product 1

HCID 184443694-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]butyric acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (0.1 g, 0.37 mmol; prepared in a manner similar to that described in Example 23), glutaric anhydride (0.042 g, 0.37 mmol) and toluene (10 ml) was heated under reflux until the starting materials were consumed (the reaction was followed by tic using a 3:1 mixture of ethyl acetate and ethanol as eluant), then it was allowed to cool to ambient temperature. The resulting solid was collected by filtration and recrystallised from ethanol to give 4-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenylcarbamoyl]butyric acid (0.08 g) as a white solid, mpt. 190–194° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 1.5–1.65 (m, 2H) (—CH2CH2CH2—), 2.0–2.25 (m, 4H) (—CH2CH2CH2—) 4.1 (s, 2H) (ArCH2—), 6.8–7.0 (m, 2H) (2×ArH), 7.5–7.8 (m, 4H) (4×ArH), 8.05 (d, 1H) (ArH), 9.45 (s, 1H) (chain CONH), 12.85 (br s, 1H) (—CO2H), 12.4 (s, 1H) (ring CONH); m/z (M−H)+. 382, 100% purity.

Workup

  1. customprepared in a manner similar to
  2. temperaturewas heated
  3. temperatureunder reflux until the starting materials
  4. customwere consumed (the reaction
  5. additiona 3:1 mixture of ethyl acetate and ethanol as eluant), then it
  6. filtrationThe resulting solid was collected by filtration
  7. customrecrystallised from ethanol

Sources & evidence

ORD record
ord-ef5fc2590dde4f5ea6944a3f3b6dc062
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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