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 2362998Notes

Reaction equation

HRID 2362998 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-74ca47a10acd467490a86505f7678c8c
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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