tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate → 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

HRID 2363016Notes

Reaction equation

HRID 2363016 reaction equation
[CH:1]1([N:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[N:6]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:46][CH2:45][C:19]4([N:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][N:21]([CH2:30][C:31]5[CH:43]=[CH:42][CH:41]=[CH:40][C:32]=5[C:33]([O:35]C(C)(C)C)=[O:34])[C:20]4=[O:44])[CH2:18][CH2:17]3)[C:5]2=[O:47])[CH2:3][CH2:2]1>Cl.O1CCOCC1>[CH:1]1([N:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[N:6]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:46][CH2:45][C:19]4([N:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][N:21]([CH2:30][C:31]5[CH:43]=[CH:42][CH:41]=[CH:40][C:32]=5[C:33]([OH:35])=[O:34])[C:20]4=[O:44])[CH2:18][CH2:17]3)[C:5]2=[O:47])[CH2:2][CH2:3]1

Participants

4

Reactant 1

HCID 58046683tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580466742-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acidYield 28.8%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (230 mg, 0.362 mmol, 1 equiv) in 4M hydrogen chloride solution in dioxane was stirred at ambient temperature for 5 h. The mixture was concentrated in vacuo and purified using preparative thin layer chromatography in 10% methanol in dichloromethane. The pure extract was treated with 4M hydrogen chloride solution in dioxane to afford the hydrogen chloride salt of the title compound as cream crystals (60 mg, 28.8%); 1H NMR (400 MHz, DMSO-d6): δ 0.86-0.90 (m, 2H); 1.01-1.06 (m, 2H); 1.98 (d, 2H, J=14.4 Hz); 2.13 (bs, 2H); 2.88-2.99 (m, 3H); 3.2 (bs, 2H); 3.65-3.73 (m, 4H); 3.91 (t, 2H, J=6.8 Hz); 4.67 (s, 2H); 4.93 (s, 2H); 6.80 (t, 1H, J=7.2 Hz); 7.01 (d, 2H, J=8.4 Hz); 7.08-7.10 (m, 2H); 7.19-7.24 (m, 2H); 7.26-7.28 (m, 1H); 7.31 (d, 1H, J=7.6 Hz); 7.43 (t, 1H, J=6.8 and 7.6 Hz); 7.55-7.59 (m, 1H); 7.92 (dd, 1H, J=1.2 Hz); 10.50 (bs, 1H); 13.2 (bs, 1H); MS for C34H37N5O4 m/z 580.12 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompurified
  3. extractionThe pure extract
  4. additionwas treated with 4M hydrogen chloride solution in dioxane

Sources & evidence

ORD record
ord-24a361f73df44be08c5ed6c9ca580a9d
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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