Formate → 3-((4-Oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid, hydrochloride salt

HRID 2362992Notes

Reaction equation

HRID 2362992 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]4([CH2:25][CH2:24]4)[C:16]3=[O:26])[CH2:8][CH2:7]2)[N:5]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][N:3]1[CH2:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[C:37]([O:39]C(C)(C)C)=[O:38].C(O)=O.C([O-])=O.[ClH:53]>O1CCOCC1>[ClH:53].[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]4([CH2:25][CH2:24]4)[C:16]3=[O:26])[CH2:8][CH2:7]2)[N:5]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:4][N:3]1[CH2:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[C:37]([OH:39])=[O:38]

Participants

6

Reactant 4

HCID 283FormateHCID 284Formic AcidHCID 313Hydrochloric AcidHCID 58046730Tert-butyl 3-((4-oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 547717533-((4-Oxo-8-(3-(2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid, hydrochloride saltYield 65%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 3-((4-oxo-8-(3-(2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.27 g, 0.435 mmol) and formic acid (4 mL) were stirred at room temperature for 20 hours. The reaction was evaporated to dryness and the residue purified by PTLC (10% methanol/dichloromethane) to give product as an oil; 1H NMR (DMSO-d6); 61.52 (m, 2H); 1.59 (m, 2H); 1.68 (d, J=13.6 Hz, 2H); 1.87 (m, 2H); 2.57-2.62 (m, 4H); 2.91 (m, 4H); 3.82 (t, J=6.4 Hz, 2H); 4.60 (s, 2H); 4.62 (s, 2H); 6.76 (t, J=7.2 Hz, 1H); 6.86 (d, J=8.4 Hz, 2H); 6.96-7.03 (m, 2H); 7.17-7.23 (m, 4H); 7.48-7.55 (m, 2H); 7.87-7.89 (m, 2H); 8.15 (s, 1H). The formate salt was dissolved in 4M hydrochloric acid in 1,4-dioxane (5 mL) and then evaporated under vacuum. The residue was dissolved in acetonitrile (5 mL) and water (5 mL) and lyophilized to give product as a white solid (0.17 g, 65%); HPLC rt 10.65 min; 1H NMR (DMSO-d6); δ1.54 (m, 2H); 1.62 (m, 2H); 1.90 (d, J=14.4 hz, 2H); 2.11 (m, 2H); 2.92-2.98 (m, 2H); 3.22 (m, 2H); 3.46-3.70 (m, 4H); 3.85 (t, J=7.2 hz, 2H); 4.64 (s, 2H); 4.65 (s, 2H); 6.79 (t, J=7.6 hz, 1H); 7.00-7.06 (m, 4H); 7.19-7.29 (m, 4H); 7.49-7.58 (m, 2H); 7.87-7.89 (m, 2H); 10.6 (br s, 1H); 13.1 (br s, 1H); MS for C34H36N4O4 m/z 565 (M+H)+.

Workup

  1. customThe reaction was evaporated to dryness
  2. customthe residue purified by PTLC (10% methanol/dichloromethane)
  3. customto give product as an oil
  4. customevaporated under vacuum
  5. dissolutionThe residue was dissolved in acetonitrile (5 mL)

Sources & evidence

ORD record
ord-a82a8a6384694377b84a9bedd9a82a75
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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