1-(Carboxymethyl)cyclopentanecarboxylic acid → 2-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-azaspiro[4.4]nonane-1,3-dione

HRID 459766Notes

Reaction equation

HRID 459766 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]([CH2:24][C:25]1([C:30](O)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1)(O)=[O:22]>>[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[N:1]1[C:21](=[O:22])[CH2:24][C:25]2([CH2:29][CH2:28][CH2:27][CH2:26]2)[C:30]1=[O:31]

Participants

3

Reactant 2

HCID 2582911-(Carboxymethyl)cyclopentanecarboxylic acidHCID 184443734-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one

Product 1

HCID 184443452-[2-Fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-azaspiro[4.4]nonane-1,3-dione

Conditions

Temperature
200 °C

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) and 1-(carboxymethyl)cyclopentane-1-carboxylic acid (0.064 g, 0.37 mmol) was heated at 200° C. in a sealed tube until the starting materials had been consumed (the reaction was followed by tlc using a 1:1 mixture of ethyl acetate and hexane as eluant). The warm mixture was poured into an ice/water mixture (10 ml) and the resulting solid was collected by filtration. The crude product was recrystallised from ethyl acetate/hexane (the hot solution required filtration to remove traces of undissolved solids) to give 2-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-azaspiro[4.4]nonane-1,3-dione (0.03 g) as an off-white solid, m.pt. 215–220° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 1.7–2.2 (m, 8H) (4× cyclopentyl CH2), 2.9 (s, 2H) (—COCH2—), 4.35 (s, 2H) (ArCH2—), 7.3–7.45 (m, 2H) (2×ArH), 7.5–7.6 (m, 1H) (ArH), 7.8–8.1 (m, 3H) (3×ArH), 8.3 (d, 1H) (ArH), 12.7 (s, 1H) (CONH); m/z (M+H)+. 406, 91.4% purity.

Workup

  1. customprepared in a manner similar to
  2. customhad been consumed (the reaction
  3. additiona 1:1 mixture of ethyl acetate and hexane as eluant)
  4. additionThe warm mixture was poured into an ice/water mixture (10 ml)
  5. filtrationthe resulting solid was collected by filtration
  6. customThe crude product was recrystallised from ethyl acetate/hexane (the hot solution required
  7. filtrationfiltration
  8. customto remove traces of undissolved solids)

Sources & evidence

ORD record
ord-e0ce36a83b9b45a9aada07aa35c09d81
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Reaction notes

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