Tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate → 3-((8-(3-(3,3-Difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

HRID 1751044Notes

Reaction equation

HRID 1751044 reaction equation
[F:1][C:2]1([F:46])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:44][CH2:43][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:20][N:19]([CH2:28][C:29]4[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=4)[C:32]([O:34]C(C)(C)C)=[O:33])[C:18]3=[O:42])[CH2:16][CH2:15]2)[C:3]1=[O:45]>Cl.O1CCOCC1>[F:46][C:2]1([F:1])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:15][CH2:16][C:17]3([N:21]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:20][N:19]([CH2:28][C:29]4[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=4)[C:32]([OH:34])=[O:33])[C:18]3=[O:42])[CH2:43][CH2:44]2)[C:3]1=[O:45]

Participants

4

Reactant 1

HCID 58046702Tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580466813-((8-(3-(3,3-Difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acidYield 42%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (210 mg, 0.333 mmol, 1 equiv) in 4M hydrogen chloride solution in dioxane was stirred at ambient temperature for 4 h. The mixture was concentrated in vacuo and the crude residue was purified using preparatory high performance liquid chromatography to afford the acetate salt of the title compound as a white solid (80 mg, 42%); 1H NMR (400 MHz, DMSO-d6): δ 1.64 (d, 2H, J=12.8 Hz); 1.87 (d, 2H, J=6 Hz); 2.40 (t, 2H, J=6.4 Hz); 2.51 (bs, 2H); 2.81 (bs, 4H); 3.80 (t, 2H, J=6.8 Hz); 4.59 (s, 2H); 4.61 (s, 2H); 6.78 (t, 1H, J=7.2 and 7.6 Hz); 6.85 (d, 2H, J=8 Hz); 7.20-7.24 (m, 3H); 7.36 (d, 1H, J=8 Hz); 7.48-7.53 (m, 2H); 7.59 (t, 1H, J=8 and 7.6 Hz); 7.71 (d, 1H, J=7.6 Hz); 7.87 (d, 1H, J=2 Hz); 7.88 (d, 2H, J=2 Hz); 12.45 (bs, 1H); MS for C32H32F2N4O4 m/z 575.03 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe crude residue was purified

Sources & evidence

ORD record
ord-790953204dce45c8b35a454b76be6068
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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