Dimethylformamide → 8-[2-[3-(3,4-Dichloro-phenyl)-1-(3,4,5-trimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl]-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione

HRID 400017Notes

Reaction equation

HRID 400017 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:28][CH2:29]CS([O-])(=O)=O)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[F:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]2[C:47]3([CH2:52][CH2:51][NH:50][CH2:49][CH2:48]3)[C:46](=[O:53])[NH:45][C:44]2=[O:54])=[CH:39][CH:38]=1.C(N(CC)C(C)C)(C)C.CN(C=O)C>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:28][CH2:29][N:50]3[CH2:49][CH2:48][C:47]4([N:43]([C:40]5[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=5)[C:44](=[O:54])[NH:45][C:46]4=[O:53])[CH2:52][CH2:51]3)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 676983301-(4-Fluorophenyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochlorideHCID 867509062-[1-(3,4,5-Trimethoxy-benzoyl)-3-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate

Product 1

HCID 538431558-[2-[3-(3,4-Dichloro-phenyl)-1-(3,4,5-trimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl]-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

Combine the 2-[3-(3,4-dichloro-phenyl)-1-(3,4,5-trimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (5.0 mmol), 1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione hydrochloride (7.5 mmol, 1.5 eq.), N,N-diisopropylethylamine (15 mmol), and DMF (8 mL). Heat the mixture at 85° C. for 48 h. Cool to ambient temperature and add ethyl acetate (100 mL). Extract with water (25 mL), 1N HCl (2×25 mL), saturated NaHCO3 (25 mL), and saturated NaCl (25 mL). Dry over MgSO4, filter, and concentrate in vacuo to obtain a residue. Purify to obtain the title compound.

Workup

  1. temperatureCool to ambient temperature
  2. extractionExtract with water (25 mL), 1N HCl (2×25 mL), saturated NaHCO3 (25 mL), and saturated NaCl (25 mL)
  3. dry with materialDry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customto obtain a residue
  7. customPurify

Sources & evidence

ORD record
ord-60e91e5d0759435583b3473b981033b1
Source dataset
uspto-grants-1998_10
Patent number
US05824690

Reaction notes

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