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Phenyl vinyl sulfone → HCID 90015531、化合物

HRID 626908
ノート
印刷プレビュー

反応式

HRID 626908 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

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

生成物 2

HCID 21705897Ammonia methanolHCID 90015531HCID 90015531、化合物収率 73.4%

試薬・触媒・溶媒 2

HCID 11246Silver acetate触媒HCID 6344Dichloromethane溶媒

実験手順

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);

後処理

  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

出典と根拠

ORDレコード
ord-ec494dd2052f4bee814d539b079cbba7
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09309254B2

反応ノート

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