Succinic anhydride → 4-(1-(3-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)-1H-pyrazol-5-yl)ethoxy)-4-oxobutanoic acid

HRID 1409406Notes

Reaction equation

HRID 1409406 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[CH:25]=[C:24]([CH:26]([OH:28])[CH3:27])[NH:23][N:22]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[O:29]1[C:33](=[O:34])[CH2:32][CH2:31][C:30]1=[O:35]>CN(C)C1C=CN=CC=1.C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[CH:25]=[C:24]([CH:26]([O:28][C:33](=[O:34])[CH2:32][CH2:31][C:30]([OH:35])=[O:29])[CH3:27])[NH:23][N:22]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

6

Reactant 2

HCID 7922Succinic anhydride2×HCID 67171867Darolutamide

Product 1

HCID 665766814-(1-(3-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-ylcarbamoyl)-1H-pyrazol-5-yl)ethoxy)-4-oxobutanoic acidYield 56.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N—((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxy-ethyl)-1H-pyrazole-3-carboxamide (1.254 mmol, 0.5 g), dihydrofuran-2,5-dione (1.504 mmol, 0.151 g) and 4-dimethylaminopyridine (0.1254 mmol, 0.015 g) were dissolved in THF (10 ml) and DMF (1 ml). The resulting mixture was stirred at RT for one day after which the temperature was raised to 50° C. for one day. The mixture was stirred at RT over the weekend. During the reaction more dihydrofuran-2,5-dione (50 mg) was added. The solvents were evaporated and the residue was dissolved in EtOAc. The organic phase was washed with 1 M HCl, separated, dried, filtered and evaporated. The crude product was purified by flash chromatography. 352 mg of the title compound was obtained. 1H-NMR (400 MHz, CDCl3): δ 1.22-1.28 (m, 3H), 1.61-1.69 (m, 3H), 2.54-2.79 (m, 4H), 4.29-4.45 (m, 2H), 4.52-4.64 (m, 1H), 5.97-6.06 (m, 1H), 6.58-6.62 (m, 1H), 6.76-6.80 (m, 1H), 7.50-7.53 (m, 1H), 7.62-7.68 (m, 1H), 7.70-7.77 (m, 1H), 7.90-8.04 (m, 2H).

Workup

  1. temperaturewas raised to 50° C. for one day
  2. stirringThe mixture was stirred at RT over the weekend
  3. additionwas added
  4. customThe solvents were evaporated
  5. dissolutionthe residue was dissolved in EtOAc
  6. washThe organic phase was washed with 1 M HCl
  7. customseparated
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-b25b2211bca94539859318981b04dac3
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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