Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate → 3-((1-(4-Fluorophenyl)-4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

HRID 1751072Notes

Reaction equation

HRID 1751072 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH2:20][N:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C:23]5([CH2:31][CH2:30]5)[C:22]4=[O:32])[CH2:14][CH2:13]3)[C:11](=[O:33])[N:10]([CH2:34][C:35]3[CH:36]=[C:37]([CH:45]=[CH:46][CH:47]=3)[C:38]([O:40]C(C)(C)C)=[O:39])[CH2:9]2)=[CH:4][CH:3]=1>C(O)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]3([CH2:13][CH2:14][N:15]([CH2:18][CH2:19][CH2:20][N:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C:23]5([CH2:30][CH2:31]5)[C:22]4=[O:32])[CH2:16][CH2:17]3)[C:11](=[O:33])[N:10]([CH2:34][C:35]3[CH:36]=[C:37]([CH:45]=[CH:46][CH:47]=3)[C:38]([OH:40])=[O:39])[CH2:9]2)=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 58046733Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 547722133-((1-(4-Fluorophenyl)-4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

To tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-8-(3-(2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)propyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (2.84 g, 0.31 mmol, 1 equiv) was added concentrated formic acid. After stirring at room temperature for 16 hours, the reaction mixture was concentrated in vacuo and purified using the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.5, gradient—1%-15% methanol in dichloromethane). The pure fractions were evaporated to dryness under reduced pressure. The pure residue was converted to the hydrogen chloride salt using 4M hydrogen chloride solution in dioxane. The resulting residue was lyophilized in acetonitrile/water (1:1) to obtain the title compound as a hydrogen chloride salt (1.8 g, 70%); 1H NMR (DMSO-d6): δ 1.50 (t, 2H, J=7.6 Hz), 1.57 (t, 2H, J=7.6 Hz), 1.70 (d, 2H, J=14 Hz), 1.83 (t, 2H, J=6.8 Hz), 2.29-2.37 (m, 2H), 2.54 (t, 2H, J=6.4 Hz), 2.87-2.89 (m, 4H), 3.80 (t, 2H, J=6.8 Hz), 4.57 (d, 4H, J=12 Hz), 6.91-7.23 (m, 8H), 7.48-7.51 (m, 2H), 7.86-7.88 (m, 2H), 8.14 (s, 1H); MS for C34H35FN4O4 m/z 583.16 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. custompurified
  3. customThe pure fractions were evaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-9ad143a234474e2f8663111daab8fab1
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

Loading…