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 1751087Notes

Reaction equation

HRID 1751087 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-dfd85f17c4e44b8eabb0bb327c4d4af1
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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