Dimethylformamide → (2S,4S)-N-{2-[4-(Diphenylmethyl)piperazin-1-yl]ethyl}-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide

HRID 373506

Reaction equation

HRID 373506 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:6][CH2:5]1.C1CCN2C(=NCCC2)CC1.CN(C)C=O.[F:39][C:40]1[CH:41]=[C:42]2[C@:49]3([C:53](=[O:54])[NH:52][C:51](=[O:55])[NH:50]3)[CH2:48][C@@H:47]([C:56](Cl)=[O:57])[O:46][C:43]2=[CH:44][CH:45]=1>>[C:11]1([CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:7]2[CH2:6][CH2:5][N:4]([CH2:3][CH2:2][NH:1][C:56]([C@@H:47]3[CH2:48][C@@:49]4([C:53](=[O:54])[NH:52][C:51](=[O:55])[NH:50]4)[C:42]4[C:43](=[CH:44][CH:45]=[C:40]([F:39])[CH:41]=4)[O:46]3)=[O:57])[CH2:9][CH2:8]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 47424562-(4-Benzhydrylpiperazino)ethaneamineHCID 57210646(2S,4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride

Product 1

HCID 24846088(2S,4S)-N-{2-[4-(Diphenylmethyl)piperazin-1-yl]ethyl}-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamideYield 65.3%

Conditions

Temperature
-30 °C

Procedure

A mixture of 1-(2-aminoethyl)-4-diphenylmethylpiperazine (10.0 g, 33.9 mmol), 1,8-diazabicyclo[5,4,0]-7-undecene (10.9 g, 71.7 mmol) and N,N-dimethylformamide (90.0 ml, 1.16 mol) was chilled to -30° C. To the mixture was added over 30 minutes a solution of (2S, 4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example 1, 10.0 g, 33.5 mmol) in N,N-dimethylformamide (90.0 ml, 1.16 mol) and the mixture was stirred for 15 hours at temperature of 15°-25° C. After distilling off the solvent, the reaction mixture was chromatographed on silica gel, eluted with CH2Cl2 /MeOH (9/1) and evaporated in vacuo to dryness to give the desired compound (12.2 g, 65.2%) as colorless amorphous substance.

Workup

  1. distillationAfter distilling off the solvent
  2. customthe reaction mixture was chromatographed on silica gel
  3. washeluted with CH2Cl2 /MeOH (9/1)
  4. customevaporated in vacuo to dryness

Sources & evidence

ORD record
ord-8e72afad75ea478c8887c507effe7f66
Source dataset
uspto-grants-1992_11
Patent number
US05164391

Linked notes

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