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

HRID 2363018Notes

Reaction equation

HRID 2363018 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[CH2:47][CH2:46][C:19]4([N:23]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)[CH2:22][N:21]([CH2:31][C:32]5[CH:33]=[C:34]([CH:42]=[CH:43][CH:44]=5)[C:35]([O:37]C(C)(C)C)=[O:36])[C:20]4=[O:45])[CH2:18][CH2:17]3)[C:5]2=[O:48])[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[CH2:47][CH2:46][C:19]4([N:23]([C:24]5[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=5)[CH2:22][N:21]([CH2:31][C:32]5[CH:33]=[C:34]([CH:42]=[CH:43][CH:44]=5)[C:35]([OH:37])=[O:36])[C:20]4=[O:45])[CH2:18][CH2:17]3)[C:5]2=[O:48])[CH2:2][CH2:3]1

Participants

4

Reactant 1

HCID 58046607tert-butyl 3-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580466143-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acidYield 36.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 3-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (166 mg, 0.254 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 (55 mg, 36.4%); 1H NMR (400 MHz, DMSO-d6): δ 0.86-0.90 (m, 2H); 1.01-1.06 (m, 2H); 1.93 (d, 2H, J=14 Hz); 2.06-2.11 (m, 2H); 2.58-2.73 (m, 2H); 2.88-2.89 (m, 1H); 3.19 (bs, 2H); 3.67-3.73 (m, 4H); 3.89 (t, 2H, J=6.8 Hz); 4.62 (s, 4H); 7.05-7.12 (m, 6H); 7.22-7.27 (m, 2H); 7.48-7.57 (m, 2H); 7.87-7.89 (m, 2H); 10.05 (bs, 1H); 13.03 (bs, 1H); MS for C34H36FN5O4 m/z 598.28 (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-1b07be9ef1f44b34b95a0e6a62502364
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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