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

HRID 2363034Notes

Reaction equation

HRID 2363034 reaction equation
[F:1][C:2]1([CH3:46])[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:41]=[CH:40][CH:39]=[CH:38][C:30]=4[C:31]([O:33]C(C)(C)C)=[O:32])[C:18]3=[O:42])[CH2:16][CH2:15]2)[C:3]1=[O:45].Cl>O1CCOCC1>[F:1][C:2]1([CH3:46])[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:41]=[CH:40][CH:39]=[CH:38][C:30]=4[C:31]([OH:33])=[O:32])[C:18]3=[O:42])[CH2:16][CH2:15]2)[C:3]1=[O:45]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58046773Tert-butyl 2-((8-(3-(3-fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580466622-((8-(3-(3-Fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To tert-butyl 2-((8-(3-(3-fluoro-3-methyl-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.1 g, 0.16 mmol) was added concentrated 4M HCl in dioxane (1.6 mL) and triethylsilane (0.02 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 (0.039 g, 40%); 1H NMR (DMSO-d6): δ 1.72 (d, 3H, J=23.2 Hz), 1.97 (d, 2H, J=14 Hz), 2.07 (br, 2H), 2.93 (t, 2H, J=10 Hz), 3.17 (br, 2H), 3.44-3.79 (m, 8H), 4.64 (s, 2H), 4.92 (s, 2H), 6.80 (t, 1H, J=7.2 Hz), 6.99 (d, 1H, J=8.4 Hz), 7.07 (d, 1H, J=8 Hz), 7.15 (t, 1H, J=7.6 Hz), 7.20-7.26 (m, 2H), 7.31 (d, 1H, J=7.6 Hz), 7.40-7.48 (m, 2H), 7.57 (t, 1H, J=7.6 Hz), 7.92 (dd, 1H, J=8 and 1.2 Hz), 10.27 (br, 1H), 13.21 (s, 1H); MS for C33H35FN4O4 m/z 571.3 (M+H)+.

Workup

  1. concentrationconcentrated 4M HCl in dioxane (1.6 mL) and triethylsilane (0.02 mL)
  2. concentrationthe reaction mixture was concentrated
  3. customisolated by preparatory TLC (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-62a4e46c0170416abdf0da34e4bf0b10
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

Loading…