Acetic Acid → 4-((3-(4-Methyl-5-(pyridin-3-ylmethylcarbamoyl)thiophen-2-yl)-2-oxoimidazolidin-1-yl)methyl)benzoic acid

HRID 560911Notes

Reaction equation

HRID 560911 reaction equation
[C:1]([C:4]1[CH:32]=[CH:31][C:7]([CH2:8][N:9]2[CH2:13][CH2:12][N:11]([C:14]3[S:18][C:17]([C:19]([NH:21][CH2:22][C:23]4[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=4)=[O:20])=[C:16]([CH3:29])[CH:15]=3)[C:10]2=[O:30])=[CH:6][CH:5]=1)(=[O:3])N.[OH-].[K+].C(O)(=[O:37])C>C(O)C.O>[CH3:29][C:16]1[CH:15]=[C:14]([N:11]2[CH2:12][CH2:13][N:9]([CH2:8][C:7]3[CH:31]=[CH:32][C:4]([C:1]([OH:3])=[O:37])=[CH:5][CH:6]=3)[C:10]2=[O:30])[S:18][C:17]=1[C:19](=[O:20])[NH:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 14797Potassium HydroxideHCID 250959275-(3-(4-carbamoylbenzyl)-2-oxoimidazolidin-1-yl)-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide

Product 1

HCID 594812304-((3-(4-Methyl-5-(pyridin-3-ylmethylcarbamoyl)thiophen-2-yl)-2-oxoimidazolidin-1-yl)methyl)benzoic acidYield 50%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 5-(3-(4-carbamoylbenzyl)-2-oxoimidazolidin-1-yl)-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide (0.16 g, 0.36 mmol) and 5 N aqueous potassium hydroxide solution (5.0 mL, 25.0 mmol) in ethanol (5 mL) was stirred at reflux for 2 h, cooled to 0° C. and acidified with glacial acetic acid to pH˜6. The mixture was diluted with water (25 mL) and extracted with dichloromethane (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with ether in hexanes to afford the title compound as a colorless solid in 50% yield (0.08 g): mp 120° C. (dec.): 1H NMR (300 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.46 (s, 1H), 8.30 (t, J=5.8 Hz, 1H), 7.93 (d, J=8.1 Hz, 2H), 7.71 (d, J=7.8 Hz, 1H), 7.44-7.32 (m, 2H), 6.24 (s, 1H), 4.47 (s, 2H), 4.39 (d, J=5.8 Hz, 2H), 3.88-3.79 (m, 2H), 3.51-3.43 (m, 2H), 2.37 (s, 3H): 13C NMR (75 MHz, DMSO-d6) δ 167.0, 162.9, 155.5, 148.8, 147.8, 142.5, 141.7, 139.0, 135.0, 130.0, 129.6, 127.7, 123.4, 119.9, 113.8, 112.1, 46.8, 42.5, 41.5, 15.7: MS (ES+) m/z 450.4 (M+1).

Workup

  1. temperatureat reflux for 2 h
  2. extractionextracted with dichloromethane (2×50 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with ether in hexanes

Sources & evidence

ORD record
ord-be7629a2c80846c48645b762b3eed654
Source dataset
uspto-grants-2011_11
Patent number
US08063084B2

Reaction notes

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