Hydrochloric Acid → 3-((8-(3-(3-Fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

HRID 2363038Notes

Reaction equation

HRID 2363038 reaction equation
[F:1][C:2]1([CH3:47])[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[CH2:45][CH2:44][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:20][N:19]([CH2:29][C:30]4[CH:31]=[C:32]([CH:40]=[CH:41][CH:42]=4)[C:33]([O:35]C(C)(C)C)=[O:34])[C:18]3=[O:43])[CH2:16][CH2:15]2)[C:3]1=[O:46].Cl>O1CCOCC1>[F:1][C:2]1([CH3:47])[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][C:25]([F:28])=[CH:26][CH:27]=4)[CH2:20][N:19]([CH2:29][C:30]4[CH:31]=[C:32]([CH:40]=[CH:41][CH:42]=4)[C:33]([OH:35])=[O:34])[C:18]3=[O:43])[CH2:44][CH2:45]2)[C:3]1=[O:46]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58046812Tert-butyl 3-((8-(3-(3-fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580467873-((8-(3-(3-Fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To tert-butyl 3-((8-(3-(3-fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.26 g, 0.4 mmol) was added concentrated 4M HCl in dioxane (4 mL) and triethylsilane (0.05 mL). After stirring at room temperature for 4 hours, the reaction mixture was concentrated, isolated by preparatory TLC (10% methanol/dichloromethane) and lyophilized with 4M HCl in dioxane (1 mL) to obtain the title compound as a hydrochloride salt (0.16 g, 64%); 1H NMR (DMSO-d6): δ 1.72 (d, 3H, J=22.4 Hz), 1.92 (d, 2H, J=13.6 Hz), 2.06 (br, 2H), 2.67 (t, 2H, J=10 Hz), 3.19 (br, 2H), 3.45-3.71 (m, 4H), 3.76 (t, 2H, J=7.2 Hz), 4.62 (s, 4H), 7.07 (d, 4H, J=6.4 Hz), 7.15 (t, 1H, J=8 Hz), 7.24 (d, 1H, J=8 Hz), 7.44-7.59 (m, 4H), 7.87 (dd, 2H, J=6.8 and 2 Hz), 10.27 (br, 1H), 13.03 (s, 1H); MS for C33H34F2N4O4 m/z 589.3 (M+H)+.

Workup

  1. concentrationconcentrated 4M HCl in dioxane (4 mL) and triethylsilane (0.05 mL)
  2. concentrationthe reaction mixture was concentrated
  3. customisolated by preparatory TLC (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-0ab6b743d8b0417ca9b0d12e3cd90d2a
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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