Phenyl vinyl sulfone → HCID 90015531, compound

HRID 626908Notes

Reaction equation

HRID 626908 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:5]=[C:4]([CH:18]=[O:19])[N:3]=1.[NH2:20][CH:21]1[CH2:25][CH2:24][NH:23][C:22]1=[O:26].[CH:27](S(C1C=CC=CC=1)(=O)=O)=[CH2:28].C1CCN2C(=NCCC2)CC1>C(Cl)Cl.C([O-])(=O)C.[Ag+]>[NH3:3].[CH3:18][OH:19].[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:15])([F:16])[F:17])=[CH:12][CH:13]=2)[N:5]=[C:4]([C:18]2[CH2:28][CH2:27][C:21]3([CH2:25][CH2:24][NH:23][C:22]3=[O:26])[N:20]=2)[N:3]=1

Participants

8

Reactant 4

HCID 79664Phenyl vinyl sulfoneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 104868053-Amino-pyrrolidin-2-oneHCID 900155544-Methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2-carbaldehyde

Product 2

HCID 21705897Ammonia methanolHCID 90015531HCID 90015531, compoundYield 73.4%

Reagents, catalysts & solvents 2

HCID 11246Silver acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

3A Molecular sieves (10 g, 5.63 mmol) were dried under vacuum then treated with a solution of 4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine-2-carbaldehyde (which may be prepared as described in Description 30) (1.5 g, 5.63 mmol) in dry DCM (45 mL), added under nitrogen, followed by 3-aminopyrrolidin-2-one (564.12 mg, 5.63 mmol). The mixture was gently stirred under N2 at ambient temp for 4 h. The reaction mixture was filtered through celite under suction and washed with DCM (5×20 ml). The filtrate was evaporated to an almost colourless oil which was dissolved in dry THF (60 mL) placed under nitrogen and treated with phenyl vinyl sulfone (947.7 mg, 5.6 mmol) then silver acetate (940.4 mg, 5.6 mmol). The mixture was wrapped in foil, stirred at ambient temperature for 3 minutes, then DBU (0.84 mL, 5.63 mmol) was added dropwise over a further 3 minutes and the mixture left to stir for 22 h. The reaction mixture was filtered through celite and washed through with THF (5×20 ml). The filtrate was evaporated to a dark residue, dried then dissolved in DCM (20 ml) and was applied to a 100 g silica cartridge which was initially eluted on a Biotage SP4 system with a gradient of methanol in ethyl acetate, then finally with 1M NH3-MeOH:EtOAc 1:9 to give 2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]-pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D31) (774 mg);

Workup

  1. dry with material3A Molecular sieves (10 g, 5.63 mmol) were dried under vacuum
  2. additionadded under nitrogen
  3. filtrationThe reaction mixture was filtered through celite under suction
  4. washwashed with DCM (5×20 ml)
  5. customThe filtrate was evaporated to an almost colourless oil which
  6. dissolutionwas dissolved in dry THF (60 mL)
  7. stirringstirred at ambient temperature for 3 minutes
  8. waitthe mixture left
  9. stirringto stir for 22 h
  10. filtrationThe reaction mixture was filtered through celite
  11. washwashed through with THF (5×20 ml)
  12. customThe filtrate was evaporated to a dark residue
  13. customdried
  14. dissolutionthen dissolved in DCM (20 ml)
  15. washwas initially eluted on a Biotage SP4 system with a gradient of methanol in ethyl acetate

Sources & evidence

ORD record
ord-ec494dd2052f4bee814d539b079cbba7
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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