Acetic Acid → 1-(4-{4-[(2S)-2-Hydroxy-3-(2-oxo-2,3-dihydro-1H-benzoimidazol-4-yloxy)-propylamino]-piperidin-1-yl}-benzenesulfonyl)-imidazolidine-2,4-dione

HRID 351715Notes

Reaction equation

HRID 351715 reaction equation
C(O)(=O)C.[NH2:5][CH2:6][C@H:7]([OH:20])[CH2:8][O:9][C:10]1[C:18]2[NH:17][C:16](=[O:19])[NH:15][C:14]=2[CH:13]=[CH:12][CH:11]=1.O=[C:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31]([S:34]([N:37]3[CH2:41][C:40](=[O:42])[NH:39][C:38]3=[O:43])(=[O:36])=[O:35])=[CH:30][CH:29]=2)[CH2:24][CH2:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN(C)C=O>[OH:20][C@H:7]([CH2:8][O:9][C:10]1[C:18]2[NH:17][C:16](=[O:19])[NH:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)[CH2:6][NH:5][CH:22]1[CH2:23][CH2:24][N:25]([C:28]2[CH:29]=[CH:30][C:31]([S:34]([N:37]3[CH2:41][C:40](=[O:42])[NH:39][C:38]3=[O:43])(=[O:36])=[O:35])=[CH:32][CH:33]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 107991054-((2S)-3-Amino-2-hydroxy-propoxy)-1,3-dihydrobenzoimidazol-2-oneHCID 227133341-[[4-(4-Oxo-1-piperidinyl)phenyl]sulfonyl]-2,4-imidazolidinedione

Product 1

HCID 102092381-(4-{4-[(2S)-2-Hydroxy-3-(2-oxo-2,3-dihydro-1H-benzoimidazol-4-yloxy)-propylamino]-piperidin-1-yl}-benzenesulfonyl)-imidazolidine-2,4-dioneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Acetic acid (0.14 mL, 2.38 mmol) was added dropwise into a mixture of 4-{[(2S)-3-amino-2-hydroxypropyl]oxy}-1,3-dihydro-2H-benzimidazol-2-one (265 mg, 1.19 mmol), 1-[[4-(4-oxo-1-piperidinyl)phenyl]sulfonyl]-2,4-imidazolidinedione (400 mg, 1.19 mmol) and N,N-dimethylformamide (5 mL). The mixture was stirred for 20 minutes and then, sodium triacetoxyborohydride (303 mg, 1.43 mmol) was added, and the new mixture was stirred at room temperature for 24 hours. The volatiles were removed in vacuo and the residue was purified by flash chromatography (dichloromethane/methyl alcohol 3/1) to produce a brown solid (256 mg, 40% yield): mp 230° C. (decomposed); 1H NMR (400 MHz, DMSO-d6): δ 1.52-1.63 (m, 2H), 2.04-2.15 (m, 2H), 2.48 (m, 2H), 2.9-3.0 (m, 2H), 3.13-3.15 (m, 1H), 3.2-3.4 (m, 3H), 4.0-4.1 (m, 5H), 4.42 (s, 2H), 6.6-6.63 (m, 2H), 6.8-6.85 (m, 1H), 7.03-7.05 (m, 2H), 7.78-7.8 (m, 2H), 10.6 (s, 1H), 10.7 (s, 1H); MS m/e 543 (M−H)+;

Workup

  1. stirringthe new mixture was stirred at room temperature for 24 hours
  2. customThe volatiles were removed in vacuo
  3. customthe residue was purified by flash chromatography (dichloromethane/methyl alcohol 3/1)

Sources & evidence

ORD record
ord-9201e2cf5268458a993638826a762ce5
Source dataset
uspto-grants-2004_06
Patent number
US06743787B2

Reaction notes

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